You searched for: Antibodies

Supplier: Bioss

Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals. MTOR directly or indirectly regulates the phosphorylation of at least 800 proteins. Functions as part of 2 structurally and functionally distinct signaling complexes mTORC1 and mTORC2 (mTOR complex 1 and 2). Activated mTORC1 up-regulates protein synthesis by phosphorylating key regulators of mRNA translation and ribosome synthesis. This includes phosphorylation of EIF4EBP1 and release of its inhibition toward the elongation initiation factor 4E (eiF4E). Moreover, phosphorylates and activates RPS6KB1 and RPS6KB2 that promote protein synthesis by modulating the activity of their downstream targets including ribosomal protein S6, eukaryotic translation initiation factor EIF4B, and the inhibitor of translation initiation PDCD4. Stimulates the pyrimidine biosynthesis pathway, both by acute regulation through RPS6KB1-mediated phosphorylation of the biosynthetic enzyme CAD, and delayed regulation, through transcriptional enhancement of the pentose phosphate pathway which produces 5-phosphoribosyl-1-pyrophosphate (PRPP), an allosteric activator of CAD at a later step in synthesis, this function is dependent on the mTORC1 complex. Regulates ribosome synthesis by activating RNA polymerase III-dependent transcription through phosphorylation and inhibition of MAF1 an RNA polymerase III-repressor. In parallel to protein synthesis, also regulates lipid synthesis through SREBF1/SREBP1 and LPIN1. To maintain energy homeostasis mTORC1 may also regulate mitochondrial biogenesis through regulation of PPARGC1A. mTORC1 also negatively regulates autophagy through phosphorylation of ULK1. Under nutrient sufficiency, phosphorylates ULK1 at 'Ser-758', disrupting the interaction with AMPK and preventing activation of ULK1. Also prevents autophagy through phosphorylation of the autophagy inhibitor DAP.

Supplier: Biotium

PAb122 binds to the C-terminus (aa370-378) of both wild type and mutated p53. When microinjected into nuclei, PAb122 blocked re-entry into the S-phase of the cell cycle. Mutation and/or allelic loss of p53 is one of the causes of a variety of mesenchymal and epithelial tumors. If it occurs in the germ line, such tumors run in families. p53 Binds to a DNA consensus sequence, the p53 response element, and it regulates normal cell growth cycle events by activating transcription of genes, involved either in progression through the cycle, or causing arrest in G1 when the genome is damaged. In most transformed and tumor cells the concentration of p53 is increased 51000 fold over the minute concentrations (1000 molecules cell) in normal cells, principally due to the increased half-life (4 h) compared to that of the wild-type (20 min). p53 Localizes in the nucleus, but is detectable at the plasma membrane during mitosis and when certain mutations modulate cytoplasmic/nuclear distribution. p53 Is the most commonly mutated gene in spontaneously occurring human cancers. Mutations arise with an average frequency of 70% but incidence varies from zero in carcinoid lung tumors to 97% in primary melanomas. High concentrations of p53 protein are transiently expressed in human epidermis and superficial dermal fibroblasts following mild ultraviolet irradiation.

CF® dyes are Biotium's next-generation fluorescent dyes. CF®640R is a far-red fluorescent dye (Ex/Em 642/662 nm) with excellent brightness, and the best photostabiity among spectrally-similar dyes.

Supplier: Biotium

PAb122 binds to the C-terminus (aa370-378) of both wild type and mutated p53. When microinjected into nuclei, PAb122 blocked re-entry into the S-phase of the cell cycle. Mutation and/or allelic loss of p53 is one of the causes of a variety of mesenchymal and epithelial tumors. If it occurs in the germ line, such tumors run in families. p53 Binds to a DNA consensus sequence, the p53 response element, and it regulates normal cell growth cycle events by activating transcription of genes, involved either in progression through the cycle, or causing arrest in G1 when the genome is damaged. In most transformed and tumor cells the concentration of p53 is increased 51000 fold over the minute concentrations (1000 molecules cell) in normal cells, principally due to the increased half-life (4 h) compared to that of the wild-type (20 min). p53 Localizes in the nucleus, but is detectable at the plasma membrane during mitosis and when certain mutations modulate cytoplasmic/nuclear distribution. p53 Is the most commonly mutated gene in spontaneously occurring human cancers. Mutations arise with an average frequency of 70% but incidence varies from zero in carcinoid lung tumors to 97% in primary melanomas. High concentrations of p53 protein are transiently expressed in human epidermis and superficial dermal fibroblasts following mild ultraviolet irradiation.

CF® dyes are Biotium's next-generation fluorescent dyes. CF®488A is a green fluorescent dye (Ex/Em 490/515 nm) with excellent brightness and photostability. The dye is minimally charged for less non-specific binding. CF®488A also is compatible with super-resolution imaging by TIRF.

Supplier: Thermo Scientific

Sphingosine Kinase (SphK) catalyzes the phosphorylation of the lipid sphingosine, creating the bioactive lipid sphingosine-1-phosphate (S1P). S1P subsequently signals through cell surface G protein-coupled receptors, as well as intracellularly, to modulate cell proliferation, survival, motility and differentiation. SphK is an important signaling enzyme which is activated by diverse agents, including growth factors that signal through receptor tyrosine kinases, agents activating G protein-coupled receptors, and immunoglobulin receptors. Two SphK isotypes, SphK-1 and SphK-2, have been cloned, and both isotypes are ubiquitously expressed. SphK-1 has been shown to mediate cell growth, prevention of apoptosis, and cellular transformation, and is upregulated in a variety of human tumors. In contrast, SphK-2 increases apoptosis, and may be responsible for phosphorylating and activating the immunosuppressive drug FTY720.

Supplier: Biotium

Laminins are large hetero-trimeric, non-collagenous glycoproteins composed of α, β, and γ chains. This MAb reacts with laminin B2/1 chain of ~210 kDa and does not cross-react with other basement membrane components or fibronectin. Its specificity was established by immunoprecipitation and immunofluorescence of human skeletal muscle and kidney with laminin chain-specific MAbs. Epithelial sheets in vivo are separated from the mesenchymal elements of the stroma by a thin layer of a specialized type of extracellular matrix termed the basement membrane (BM). This structure consists of individual components, some of which are ubiquitous in BMs and some are not. The ubiquitous ones comprise laminin (LN), entactin/nidogen (EN), collagen type IV (CIV), and large heparan sulfate proteoglycan (HSPG), which interact specifically with each other to form a continuous and regular BM. Alterations of BM integrity, from local discontinuities up to complete loss, are described in many types of human and animal epithelial neoplasms. This MAb stains uniformly all human and murine basement membranes.

CF® dyes are Biotium's next-generation fluorescent dyes. CF®405S is a blue fluorescent dye (Ex/Em 404/431 nm) with superior brightness compared to other blue dyes; it is also compatible with super-resolution imaging by SIM. Note: Conjugates of blue fluorescent dyes are not recommended for detecting low abundance targets, because blue dyes have lower fluorescence and can give higher non-specific background than other dye colors.

Supplier: Bioss

Tumor suppressor serine/threonine-protein kinase that controls the activity of AMP-activated protein kinase (AMPK) family members, thereby playing a role in various processes such as cell metabolism, cell polarity, apoptosis and DNA damage response. Acts by phosphorylating the T-loop of AMPK family proteins, thus promoting their activity: phosphorylates PRKAA1, PRKAA2, BRSK1, BRSK2, MARK1, MARK2, MARK3, MARK4, NUAK1, NUAK2, SIK1, SIK2, SIK3 and SNRK but not MELK. Also phosphorylates non-AMPK family proteins such as STRADA, PTEN and possibly p53/TP53. Acts as a key upstream regulator of AMPK by mediating phosphorylation and activation of AMPK catalytic subunits PRKAA1 and PRKAA2 and thereby regulates processes including: inhibition of signaling pathways that promote cell growth and proliferation when energy levels are low, glucose homeostasis in liver, activation of autophagy when cells undergo nutrient deprivation, and B-cell differentiation in the germinal center in response to DNA damage. Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton. Required for cortical neuron polarization by mediating phosphorylation and activation of BRSK1 and BRSK2, leading to axon initiation and specification. Involved in DNA damage response: interacts with p53/TP53 and recruited to the CDKN1A/WAF1 promoter to participate in transcription activation. Able to phosphorylate p53/TP53; the relevance of such result in vivo is however unclear and phosphorylation may be indirect and mediated by downstream STK11/LKB1 kinase NUAK1. Also acts as a mediator of p53/TP53-dependent apoptosis via interaction with p53/TP53: translocates to the mitochondrion during apoptosis and regulates p53/TP53-dependent apoptosis pathways. In vein endothelial cells, inhibits PI3K/Akt signaling activity and thus induces apoptosis in response to the oxidant peroxynitrite (in vitro). Regulates UV radiation-induced DNA damage response mediated by CDKN1A.

Supplier: Bioss

Stress-activated, pro-apoptotic kinase which, following caspase-cleavage, enters the nucleus and induces chromatin condensation followed by internucleosomal DNA fragmentation. Key component of the Hippo signaling pathway which plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. The core of this pathway is composed of a kinase cascade wherein STK3/MST2 and STK4/MST1, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ. Phosphorylation of YAP1 by LATS2 inhibits its translocation into the nucleus to regulate cellular genes important for cell proliferation, cell death, and cell migration. STK3/MST2 and STK4/MST1 are required to repress proliferation of mature hepatocytes, to prevent activation of facultative adult liver stem cells (oval cells), and to inhibit tumor formation (By similarity). Phosphorylates 'Ser-14' of histone H2B (H2BS14ph) during apoptosis. Phosphorylates FOXO3 upon oxidative stress, which results in its nuclear translocation and cell death initiation. Phosphorylates MOBKL1A, MOBKL1B and RASSF2. Phosphorylates TNNI3 (cardiac Tn-I) and alters its binding affinity to TNNC1 (cardiac Tn-C) and TNNT2 (cardiac Tn-T). Phosphorylates FOXO1 on 'Ser-212' and regulates its activation and stimulates transcription of PMAIP1 in a FOXO1-dependent manner. Phosphorylates SIRT1 and inhibits SIRT1-mediated p53/TP53 deacetylation, thereby promoting p53/TP53 dependent transcription and apoptosis upon DNA damage. Acts as an inhibitor of PKB/AKT1. Phosphorylates AR on 'Ser-650' and suppresses its activity by intersecting with PKB/AKT1 signaling and antagonizing formation of AR-chromatin complexes.

Supplier: Prosci

ILF3 may facilitate double-stranded RNA-regulated gene expression at the level of post-transcription. ILF3 can act as a translation inhibitory protein which binds to coding sequences of acid beta-glucosidase (GCase) and other mRNAs and functions at the initiation phase of GCase mRNA translation, probably by inhibiting its binding to polysomes. ILF3 can regulate protein arginine N-methyltransferase 1 activity. ILF3 may regulate transcription of the IL2 gene during T-cell activation. It can promote the formation of stable DNA-dependent protein kinase holoenzyme complexes on DNA.Nuclear factor of activated T-cells (NFAT) is a transcription factor required for T-cell expression of interleukin 2. NFAT binds to a sequence in the IL2 enhancer known as the antigen receptor response element 2. In addition, NFAT can bind RNA and is an essential component for encapsidation and protein priming of hepatitis B viral polymerase. NFAT is a heterodimer of 45 kDa and 90 kDa proteins, the larger of which is the product of this gene. The encoded protein, which is primarily localized to ribosomes, probably regulates transcription at the level of mRNA elongation. At least three transcript variants encoding three different isoforms have been found for this gene.Nuclear factor of activated T-cells (NFAT) is a transcription factor required for T-cell expression of interleukin 2. NFAT binds to a sequence in the IL2 enhancer known as the antigen receptor response element 2. In addition, NFAT can bind RNA and is an essential component for encapsidation and protein priming of hepatitis B viral polymerase. NFAT is a heterodimer of 45 kDa and 90 kDa proteins, the larger of which is the product of this gene. The encoded protein, which is primarily localized to ribosomes, probably regulates transcription at the level of mRNA elongation. At least three transcript variants encoding three different isoforms have been found for this gene.

Supplier: Prosci

MBD1 belongs to a family of nuclear proteins related by the presence in each of a methyl-CpG binding domain (MBD). Each of these proteins, with the exception of MBD3, is capable of binding specifically to methylated DNA. MBD1 can also repress transcription from methylated gene promoters. Five transcript variants of the MBD1 are generated by alternative splicing resulting in protein isoforms that contain one MBD domain, two to three cysteine-rich (CXXC) domains, and some differences in the COOH terminus. All five transcript variants repress transcription from methylated promoters; in addition, variants with three CXXC domains also repress unmethylated promoter activity. DNA methylation is the major modification of eukaryotic genomes and plays an essential role in mammalian development. Human proteins MECP2, MBD1, MBD2, MBD3, and MBD4 comprise a family of nuclear proteins related by the presence in each of a methyl-CpG binding domain (MBD). Each of these proteins, with the exception of MBD3, is capable of binding specifically to methylated DNA. MECP2, MBD1 and MBD2 can also repress transcription from methylated gene promoters. Five transcript variants of the MBD1 are generated by alternative splicing resulting in protein isoforms that contain one MBD domain, two to three cysteine-rich (CXXC) domains, and some differences in the COOH terminus. All five transcript variants repress transcription from methylated promoters; in addition, variants with three CXXC domains also repress unmethylated promoter activity. MBD1 and MBD2 map very close to each other on chromosome 18q21.DNA methylation is the major modification of eukaryotic genomes and plays an essential role in mammalian development. Human proteins MECP2, MBD1, MBD2, MBD3, and MBD4 comprise a family of nuclear proteins related by the presence in each of a methyl-CpG binding domain (MBD). Each of these proteins, with the exception of MBD3, is capable of binding specifically to methylated DNA. MECP2, MBD1 and MBD2 can also repress transcription from methylated gene promoters. Five transcript variants of the MBD1 are generated by alternative splicing resulting in protein isoforms that contain one MBD domain, two to three cysteine-rich (CXXC) domains, and some differences in the COOH terminus. All five transcript variants repress transcription from methylated promoters; in addition, variants with three CXXC domains also repress unmethylated promoter activity. MBD1 and MBD2 map very close to each other on chromosome 18q21.

Supplier: Bioss

NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to many biological processes such as inflammation, immunity, differentiation, cell growth, tumorigenesis and apoptosis. NF-kappa-B is a homo- or heterodimeric complex formed by the Rel-like domain-containing proteins RELA/p65, RELB, NFKB1/p15, NFKB1/p5, REL and NFKB2/p52 and the heterodimeric p65-p5 complex appears to be most abundant one. The dimers bind at kappa-B sites in the DNA of their target genes and the individual dimers have distinct preferences for different kappa-B sites that they can bind with distinguishable affinity and specificity. Different dimer combinations act as transcriptional activators or repressors, respectively. NF-kappa-B is controlled by various mechanisms of post-translational modification and subcellular compartmentalization as well as by interactions with other cofactors or corepressors. NF-kappa-B complexes are held in the cytoplasm in an inactive state complexed with members of the NF-kappa-B inhibitor (I-kappa-B) family. In a conventional activation pathway, I-kappa-B is phosphorylated by I-kappa-B kinases (IKKs) in response to different activators, subsequently degraded thus liberating the active NF-kappa-B complex which translocates to the nucleus. NF-kappa-B heterodimeric p65-p5 and p65-c-Rel complexes are transcriptional activators. The NF-kappa-B p65-p65 complex appears to be involved in invasin-mediated activation of IL-8 expression. The inhibitory effect of I-kappa-B upon NF-kappa-B the cytoplasm is exerted primarily through the interaction with p65. p65 shows a weak DNA-binding site which could contribute directly to DNA binding in the NF-kappa-B complex. Associates with chromatin at the NF-kappa-B promoter region via association with DDX1.

Supplier: Rockland Immunochemical

Rat IgG1 isotype control can be utilized as a control or standard reagent in Western Blotting, Flow Cytometry, and ELISA experiments where determination of sample isotype is important. Specific conditions should be optimized by user.

Supplier: Bioss

Nuclear receptor that binds DNA as a monomer to ROR response elements (RORE) containing a single core motif half-site 5'-AGGTCA-3' preceded by a short A-T-rich sequence. Key regulator of embryonic development, cellular differentiation, immunity, circadian rhythm as well as lipid, steroid, xenobiotics and glucose metabolism. Considered to have intrinsic transcriptional activity, have some natural ligands like oxysterols that act as agonists (25-hydroxycholesterol) or inverse agonists (7-oxygenated sterols), enhancing or repressing the transcriptional activity, respectively. Recruits distinct combinations of cofactors to target genes regulatory regions to modulate their transcriptional expression, depending on the tissue, time and promoter contexts. Regulates genes involved in photoreceptor development including OPN1SW, OPN1SM and ARR3 and skeletal muscle development with MYOD1. Required for proper cerebellum development, regulates SHH gene expression, among others, to induce granule cells proliferation as well as expression of genes involved in calcium-mediated signal transduction. Regulates the circadian expression of several clock genes, including CLOCK, ARNTL/BMAL1, NPAS2 and CRY1. Competes with NR1D1 for binding to their shared DNA response element on some clock genes such as ARNTL/BMAL1, CRY1 and NR1D1 itself, resulting in NR1D1-mediated repression or RORA-mediated activation of clock genes expression, leading to the circadian pattern of clock genes expression. Therefore influences the period length and stability of the clock. Regulates genes involved in lipid metabolism such as apolipoproteins APOA1, APOA5, APOC3 and PPARG. In liver, has specific and redundant functions with RORC as positive or negative modulator of expression of genes encoding phase I and phase II proteins involved in the metabolism of lipids, steroids and xenobiotics, such as CYP7B1 and SULT2A1.

Supplier: Thermo Scientific

Poly(ADP-ribosyl)ation is an immediate DNA-damage-dependent post-translational modification of histones and other nuclear proteins that contributes to the survival of injured proliferating cells. Poly(ADP-ribose) polymerases (PARPs) now constitute a large family of 18 proteins, encoded by different genes and displaying a conserved catalytic domain in which PARP-1 (113 kDa), the founding member, and PARP-2 (62 kDa) are so far the sole enzymes whose catalytic activity has been shown to be immediately stimulated by DNA strand breaks. A large repertoire of sequences encoding novel PARPs now extends considerably the field of poly(ADP-ribosyl)ation reactions to various aspects of the cell biology including cell proliferation and cell death. Some of these new members interact with each other, share common partners and common subcellular localizations suggesting possible fine tuning in the regulation of this post-translational modification of proteins.

Supplier: Bioss

IFN-induced dsRNA-dependent serine/threonine-protein kinase which plays a key role in the innate immune response to viral infection and is also involved in the regulation of signal transduction, apoptosis, cell proliferation and differentiation. Exerts its antiviral activity on a wide range of DNA and RNA viruses including hepatitis C virus (HCV), hepatitis B virus (HBV), measles virus (MV) and herpes simplex virus 1 (HHV-1). Inhibits viral replication via phosphorylation of the alpha subunit of eukaryotic initiation factor 2 (EIF2S1), this phosphorylation impairs the recycling of EIF2S1 between successive rounds of initiation leading to inhibition of translation which eventually results in shutdown of cellular and viral protein synthesis. Also phosphorylates other substrates including p53/TP53, PPP2R5A, DHX9, ILF3, IRS1 and the HHV-1 viral protein US11. In addition to serine/threonine-protein kinase activity, also has tyrosine-protein kinase activity and phosphorylates CDK1 at 'Tyr-4' upon DNA damage, facilitating its ubiquitination and proteosomal degradation. Either as an adapter protein and/or via its kinase activity, can regulate various signaling pathways (p38 MAP kinase, NF-kappa-B and insulin signaling pathways) and transcription factors (JUN, STAT1, STAT3, IRF1, ATF3) involved in the expression of genes encoding proinflammatory cytokines and IFNs. Activates the NF-kappa-B pathway via interaction with IKBKB and TRAF family of proteins and activates the p38 MAP kinase pathway via interaction with MAP2K6. Can act as both a positive and negative regulator of the insulin signaling pathway (ISP). Negatively regulates ISP by inducing the inhibitory phosphorylation of insulin receptor substrate 1 (IRS1) at 'Ser-312' and positively regulates ISP via phosphorylation of PPP2R5A which activates FOXO1, which in turn up-regulates the expression of insulin receptor substrate 2 (IRS2).

Supplier: Genetex

BRCA1 (breast and ovarian cancer susceptibility protein 1) is a RING finger protein containing a BRCT domain. BRCA1 exists as a heterodimer with 22 possible isoforms. The full length protein has a reported molecular weight of 208 kD. BRCA1 localizes to the mitotic spindle microtubules, centriole walls, pericentriolar fibers at centrosomes. Unphosphorylated BRCA1 localizes on chromosomes from metaphase through telophase; phosphorylated BRCA1 resides in inner chromosomal structure, centrosome, cleavage furrow during prophase through telophase, and relocalizes to the perinuclear region when cells are subjected to IR or UV radiation in S phase. BRCA1 acts as a tumor suppressor and can function as a secreted growth inhibitory protein, participate in transcription coupled repair of oxidative DNA damage, X-chromosome inactivation, and can function as a E3 ubiquitin ligase. BRCA1 can be transcriptionally downregulated by Ets-2, Brg-1, and Hmga-1. BRCA1 can be modified by glycosylation, ubiquitination and phosphorylation by CDK4, ATM/ATR, cdk2, and hChk2. The BRCA1 protein has been reported to interact with RNA polymerase II holoenzyme and BARD1. BRCA1 contains at least two nuclear localization signals and is proposed to be a tumor suppressor protein. It is a serine phosphoprotein that undergoes hyperphosphorylation during late G1 and S phases of the cell cycle and is transiently dephosphorylated early after M phase. BRCA1 protein alters in a qualitative and quantitative manner during cell cycle progression. The amount of BRCA1 protein is highest during S phase and remains elevated toward G2 / M, before it declines in early G1 phase. Inherited loss of BRCA1 function confers an increased susceptibility for both breast and ovarian cancer.

Supplier: Bioss

IFN-induced dsRNA-dependent serine/threonine-protein kinase which plays a key role in the innate immune response to viral infection and is also involved in the regulation of signal transduction, apoptosis, cell proliferation and differentiation. Exerts its antiviral activity on a wide range of DNA and RNA viruses including hepatitis C virus (HCV), hepatitis B virus (HBV), measles virus (MV) and herpes simplex virus 1 (HHV-1). Inhibits viral replication via phosphorylation of the alpha subunit of eukaryotic initiation factor 2 (EIF2S1), this phosphorylation impairs the recycling of EIF2S1 between successive rounds of initiation leading to inhibition of translation which eventually results in shutdown of cellular and viral protein synthesis. Also phosphorylates other substrates including p53/TP53, PPP2R5A, DHX9, ILF3, IRS1 and the HHV-1 viral protein US11. In addition to serine/threonine-protein kinase activity, also has tyrosine-protein kinase activity and phosphorylates CDK1 at 'Tyr-4' upon DNA damage, facilitating its ubiquitination and proteosomal degradation. Either as an adapter protein and/or via its kinase activity, can regulate various signaling pathways (p38 MAP kinase, NF-kappa-B and insulin signaling pathways) and transcription factors (JUN, STAT1, STAT3, IRF1, ATF3) involved in the expression of genes encoding proinflammatory cytokines and IFNs. Activates the NF-kappa-B pathway via interaction with IKBKB and TRAF family of proteins and activates the p38 MAP kinase pathway via interaction with MAP2K6. Can act as both a positive and negative regulator of the insulin signaling pathway (ISP). Negatively regulates ISP by inducing the inhibitory phosphorylation of insulin receptor substrate 1 (IRS1) at 'Ser-312' and positively regulates ISP via phosphorylation of PPP2R5A which activates FOXO1, which in turn up-regulates the expression of insulin receptor substrate 2 (IRS2).

Supplier: Bioss

Glucagon plays a key role in glucose metabolism and homeostasis. Regulates blood glucose by increasing gluconeogenesis and decreasing glycolysis. A counterregulatory hormone of insulin, raises plasma glucose levels in response to insulin-induced hypoglycemia. Plays an important role in initiating and maintaining hyperglycemic conditions in diabetes. GLP-1 is a potent stimulator of glucose-dependent insulin release. Play important roles on gastric motility and the suppression of plasma glucagon levels. May be involved in the suppression of satiety and stimulation of glucose disposal in peripheral tissues, independent of the actions of insulin. Have growth-promoting activities on intestinal epithelium. May also regulate the hypothalamic pituitary axis (HPA) via effects on LH, TSH, CRH, oxytocin, and vasopressin secretion. Increases islet mass through stimulation of islet neogenesis and pancreatic beta cell proliferation. Inhibits beta cell apoptosis. GLP-2 stimulates intestinal growth and up-regulates villus height in the small intestine, concomitant with increased crypt cell proliferation and decreased enterocyte apoptosis. The gastrointestinal tract, from the stomach to the colon is the principal target for GLP-2 action. Plays a key role in nutrient homeostasis, enhancing nutrient assimilation through enhanced gastrointestinal function, as well as increasing nutrient disposal. Stimulates intestinal glucose transport and decreases mucosal permeability. Oxyntomodulin significantly reduces food intake. Inhibits gastric emptying in humans. Suppression of gastric emptying may lead to increased gastric distension, which may contribute to satiety by causing a sensation of fullness. Glicentin may modulate gastric acid secretion and the gastro-pyloro-duodenal activity. May play an important role in intestinal mucosal growth in the early period of life.

Supplier: Bioss

Glucagon plays a key role in glucose metabolism and homeostasis. Regulates blood glucose by increasing gluconeogenesis and decreasing glycolysis. A counterregulatory hormone of insulin, raises plasma glucose levels in response to insulin-induced hypoglycemia. Plays an important role in initiating and maintaining hyperglycemic conditions in diabetes. GLP-1 is a potent stimulator of glucose-dependent insulin release. Play important roles on gastric motility and the suppression of plasma glucagon levels. May be involved in the suppression of satiety and stimulation of glucose disposal in peripheral tissues, independent of the actions of insulin. Have growth-promoting activities on intestinal epithelium. May also regulate the hypothalamic pituitary axis (HPA) via effects on LH, TSH, CRH, oxytocin, and vasopressin secretion. Increases islet mass through stimulation of islet neogenesis and pancreatic beta cell proliferation. Inhibits beta cell apoptosis. GLP-2 stimulates intestinal growth and up-regulates villus height in the small intestine, concomitant with increased crypt cell proliferation and decreased enterocyte apoptosis. The gastrointestinal tract, from the stomach to the colon is the principal target for GLP-2 action. Plays a key role in nutrient homeostasis, enhancing nutrient assimilation through enhanced gastrointestinal function, as well as increasing nutrient disposal. Stimulates intestinal glucose transport and decreases mucosal permeability. Oxyntomodulin significantly reduces food intake. Inhibits gastric emptying in humans. Suppression of gastric emptying may lead to increased gastric distension, which may contribute to satiety by causing a sensation of fullness. Glicentin may modulate gastric acid secretion and the gastro-pyloro-duodenal activity. May play an important role in intestinal mucosal growth in the early period of life.

Supplier: Bioss

Glucagon plays a key role in glucose metabolism and homeostasis. Regulates blood glucose by increasing gluconeogenesis and decreasing glycolysis. A counterregulatory hormone of insulin, raises plasma glucose levels in response to insulin-induced hypoglycemia. Plays an important role in initiating and maintaining hyperglycemic conditions in diabetes. GLP-1 is a potent stimulator of glucose-dependent insulin release. Play important roles on gastric motility and the suppression of plasma glucagon levels. May be involved in the suppression of satiety and stimulation of glucose disposal in peripheral tissues, independent of the actions of insulin. Have growth-promoting activities on intestinal epithelium. May also regulate the hypothalamic pituitary axis (HPA) via effects on LH, TSH, CRH, oxytocin, and vasopressin secretion. Increases islet mass through stimulation of islet neogenesis and pancreatic beta cell proliferation. Inhibits beta cell apoptosis. GLP-2 stimulates intestinal growth and up-regulates villus height in the small intestine, concomitant with increased crypt cell proliferation and decreased enterocyte apoptosis. The gastrointestinal tract, from the stomach to the colon is the principal target for GLP-2 action. Plays a key role in nutrient homeostasis, enhancing nutrient assimilation through enhanced gastrointestinal function, as well as increasing nutrient disposal. Stimulates intestinal glucose transport and decreases mucosal permeability. Oxyntomodulin significantly reduces food intake. Inhibits gastric emptying in humans. Suppression of gastric emptying may lead to increased gastric distension, which may contribute to satiety by causing a sensation of fullness. Glicentin may modulate gastric acid secretion and the gastro-pyloro-duodenal activity. May play an important role in intestinal mucosal growth in the early period of life.

Supplier: Bioss

Serine/threonine kinase that plays an essential role in regulating inflammatory responses to viral infection, through the activation of the type I IFN, NF-kappa-B and STAT signaling. Also involved in TNFA and inflammatory cytokines, like Interleukin-1, signaling. Following activation of viral RNA sensors, such as RIG-I-like receptors, associates with DDX3X and phosphorylates interferon regulatory factors (IRFs), IRF3 and IRF7, as well as DDX3X. This activity allows subsequent homodimerization and nuclear translocation of the IRF3 leading to transcriptional activation of pro-inflammatory and antiviral genes including IFNB. In order to establish such an antiviral state, IKBKE forms several different complexes whose composition depends on the type of cell and cellular stimuli. Thus, several scaffolding molecules including IPS1/MAVS, TANK, AZI2/NAP1 or TBKBP1/SINTBAD can be recruited to the IKBKE-containing-complexes. Activated by polyubiquitination in response to TNFA and interleukin-1, regulates the NF-kappa-B signaling pathway through, at least, the phosphorylation of CYLD. Phosphorylates inhibitors of NF-kappa-B thus leading to the dissociation of the inhibitor/NF-kappa-B complex and ultimately the degradation of the inhibitor. In addition, is also required for the induction of a subset of ISGs which displays antiviral activity, may be through the phosphorylation of STAT1 at 'Ser-708'. Phosphorylation of STAT1 at 'Ser-708' seems also to promote the assembly and DNA binding of ISGF3 (STAT1:STAT2:IRF9) complexes compared to GAF (STAT1:STAT1) complexes, in this way regulating the balance between type I and type II IFN responses. Protects cells against DNA damage-induced cell death. Also plays an important role in energy balance regulation by sustaining a state of chronic, low-grade inflammation in obesity, wich leads to a negative impact on insulin sensitivity. Phosphorylates AKT1.

Supplier: Bioss

Serine/threonine kinase that plays an essential role in regulating inflammatory responses to viral infection, through the activation of the type I IFN, NF-kappa-B and STAT signaling. Also involved in TNFA and inflammatory cytokines, like Interleukin-1, signaling. Following activation of viral RNA sensors, such as RIG-I-like receptors, associates with DDX3X and phosphorylates interferon regulatory factors (IRFs), IRF3 and IRF7, as well as DDX3X. This activity allows subsequent homodimerization and nuclear translocation of the IRF3 leading to transcriptional activation of pro-inflammatory and antiviral genes including IFNB. In order to establish such an antiviral state, IKBKE forms several different complexes whose composition depends on the type of cell and cellular stimuli. Thus, several scaffolding molecules including IPS1/MAVS, TANK, AZI2/NAP1 or TBKBP1/SINTBAD can be recruited to the IKBKE-containing-complexes. Activated by polyubiquitination in response to TNFA and interleukin-1, regulates the NF-kappa-B signaling pathway through, at least, the phosphorylation of CYLD. Phosphorylates inhibitors of NF-kappa-B thus leading to the dissociation of the inhibitor/NF-kappa-B complex and ultimately the degradation of the inhibitor. In addition, is also required for the induction of a subset of ISGs which displays antiviral activity, may be through the phosphorylation of STAT1 at 'Ser-708'. Phosphorylation of STAT1 at 'Ser-708' seems also to promote the assembly and DNA binding of ISGF3 (STAT1:STAT2:IRF9) complexes compared to GAF (STAT1:STAT1) complexes, in this way regulating the balance between type I and type II IFN responses. Protects cells against DNA damage-induced cell death. Also plays an important role in energy balance regulation by sustaining a state of chronic, low-grade inflammation in obesity, wich leads to a negative impact on insulin sensitivity. Phosphorylates AKT1.

Supplier: Bioss

Stress-activated serine/threonine-protein kinase involved in cytokines production, endocytosis, reorganization of the cytoskeleton, cell migration, cell cycle control, chromatin remodeling, DNA damage response and transcriptional regulation. Following stress, it is phosphorylated and activated by MAP kinase p38-alpha/MAPK14, leading to phosphorylation of substrates. Phosphorylates serine in the peptide sequence, Hyd-X-R-X(2)-S, where Hyd is a large hydrophobic residue. Phosphorylates ALOX5, CDC25B, CDC25C, ELAVL1, HNRNPA, HSF1, HSP27/HSPB1, KRT18, KRT2, LIMK1, LSP1, PABPC1, PARN, PDE4A, RCSD1, RPS6KA3, TAB3 and TTP/ZFP36. Mediates phosphorylation of HSP27/HSPB1 in response to stress, leading to dissociate HSP27/HSPB1 from large small heat-shock protein (sHsps) oligomers and impair their chaperone activities and ability to protect against oxidative stress effectively. Involved in inflammatory response by regulating tumor necrosis factor (TNF) and IL6 production post-transcriptionally: acts by phosphorylating AU-rich elements (AREs)-binding proteins ELAVL1, HNRNPA, PABPC1 and TTP/ZFP36, leading to regulate the stability and translation of TNF and IL6 mRNAs. Phosphorylation of TTP/ZFP36, a major post-transcriptional regulator of TNF, promotes its binding to 14-3-3 proteins and reduces its ARE mRNA affinity leading to inhibition of dependent degradation of ARE-containing transcript. Also involved in late G2/M checkpoint following DNA damage through a process of post-transcriptional mRNA stabilization: following DNA damage, relocalizes from nucleus to cytoplasm and phosphorylates HNRNPA and PARN, leading to stabilize GADD45A mRNA. Involved in toll-like receptor signaling pathway (TLR) in dendritic cells: required for acute TLR-induced macropinocytosis by phosphorylating and activating RPS6KA3.

Supplier: Bioss

Stress-activated serine/threonine-protein kinase involved in cytokines production, endocytosis, reorganization of the cytoskeleton, cell migration, cell cycle control, chromatin remodeling, DNA damage response and transcriptional regulation. Following stress, it is phosphorylated and activated by MAP kinase p38-alpha/MAPK14, leading to phosphorylation of substrates. Phosphorylates serine in the peptide sequence, Hyd-X-R-X(2)-S, where Hyd is a large hydrophobic residue. Phosphorylates ALOX5, CDC25B, CDC25C, ELAVL1, HNRNPA, HSF1, HSP27/HSPB1, KRT18, KRT2, LIMK1, LSP1, PABPC1, PARN, PDE4A, RCSD1, RPS6KA3, TAB3 and TTP/ZFP36. Mediates phosphorylation of HSP27/HSPB1 in response to stress, leading to dissociate HSP27/HSPB1 from large small heat-shock protein (sHsps) oligomers and impair their chaperone activities and ability to protect against oxidative stress effectively. Involved in inflammatory response by regulating tumor necrosis factor (TNF) and IL6 production post-transcriptionally: acts by phosphorylating AU-rich elements (AREs)-binding proteins ELAVL1, HNRNPA, PABPC1 and TTP/ZFP36, leading to regulate the stability and translation of TNF and IL6 mRNAs. Phosphorylation of TTP/ZFP36, a major post-transcriptional regulator of TNF, promotes its binding to 14-3-3 proteins and reduces its ARE mRNA affinity leading to inhibition of dependent degradation of ARE-containing transcript. Also involved in late G2/M checkpoint following DNA damage through a process of post-transcriptional mRNA stabilization: following DNA damage, relocalizes from nucleus to cytoplasm and phosphorylates HNRNPA and PARN, leading to stabilize GADD45A mRNA. Involved in toll-like receptor signaling pathway (TLR) in dendritic cells: required for acute TLR-induced macropinocytosis by phosphorylating and activating RPS6KA3.

Supplier: Bioss

Receptor tyrosine kinase which mediates the pleiotropic actions of insulin. Binding of insulin leads to phosphorylation of several intracellular substrates, including, insulin receptor substrates (IRS1, 2, 3, 4), SHC, GAB1, CBL and other signaling intermediates. Each of these phosphorylated proteins serve as docking proteins for other signaling proteins that contain Src-homology-2 domains (SH2 domain) that specifically recognize different phosphotyrosines residues, including the p85 regulatory subunit of PI3K and SHP2. Phosphorylation of IRSs proteins lead to the activation of two main signaling pathways: the PI3K-AKT/PKB pathway, which is responsible for most of the metabolic actions of insulin, and the Ras-MAPK pathway, which regulates expression of some genes and cooperates with the PI3K pathway to control cell growth and differentiation. Binding of the SH2 domains of PI3K to phosphotyrosines on IRS1 leads to the activation of PI3K and the generation of phosphatidylinositol-(3, 4, 5)-triphosphate (PIP3), a lipid second messenger, which activates several PIP3-dependent serine/threonine kinases, such as PDPK1 and subsequently AKT/PKB. The net effect of this pathway is to produce a translocation of the glucose transporter SLC2A4/GLUT4 from cytoplasmic vesicles to the cell membrane to facilitate glucose transport. Moreover, upon insulin stimulation, activated AKT/PKB is responsible for: anti-apoptotic effect of insulin by inducing phosphorylation of BAD; regulates the expression of gluconeogenic and lipogenic enzymes by controlling the activity of the winged helix or forkhead (FOX) class of transcription factors. Another pathway regulated by PI3K-AKT/PKB activation is mTORC1 signaling pathway which regulates cell growth and metabolism and integrates signals from insulin. AKT mediates insulin-stimulated protein synthesis by phosphorylating TSC2 thereby activating mTORC1 pathway.

Supplier: Bioss

Receptor tyrosine kinase which mediates the pleiotropic actions of insulin. Binding of insulin leads to phosphorylation of several intracellular substrates, including, insulin receptor substrates (IRS1, 2, 3, 4), SHC, GAB1, CBL and other signaling intermediates. Each of these phosphorylated proteins serve as docking proteins for other signaling proteins that contain Src-homology-2 domains (SH2 domain) that specifically recognize different phosphotyrosines residues, including the p85 regulatory subunit of PI3K and SHP2. Phosphorylation of IRSs proteins lead to the activation of two main signaling pathways: the PI3K-AKT/PKB pathway, which is responsible for most of the metabolic actions of insulin, and the Ras-MAPK pathway, which regulates expression of some genes and cooperates with the PI3K pathway to control cell growth and differentiation. Binding of the SH2 domains of PI3K to phosphotyrosines on IRS1 leads to the activation of PI3K and the generation of phosphatidylinositol-(3, 4, 5)-triphosphate (PIP3), a lipid second messenger, which activates several PIP3-dependent serine/threonine kinases, such as PDPK1 and subsequently AKT/PKB. The net effect of this pathway is to produce a translocation of the glucose transporter SLC2A4/GLUT4 from cytoplasmic vesicles to the cell membrane to facilitate glucose transport. Moreover, upon insulin stimulation, activated AKT/PKB is responsible for: anti-apoptotic effect of insulin by inducing phosphorylation of BAD; regulates the expression of gluconeogenic and lipogenic enzymes by controlling the activity of the winged helix or forkhead (FOX) class of transcription factors. Another pathway regulated by PI3K-AKT/PKB activation is mTORC1 signaling pathway which regulates cell growth and metabolism and integrates signals from insulin. AKT mediates insulin-stimulated protein synthesis by phosphorylating TSC2 thereby activating mTORC1 pathway.

Supplier: Thermo Scientific

Protein kinases are enzymes that transfer a phosphate group from a phosphate donor, generally the g phosphate of ATP, onto an acceptor amino acid in a substrate protein. By this basic mechanism, protein kinases mediate most of the signal transduction in eukaryotic cells, regulating cellular metabolism, transcription, cell cycle progression, cytoskeletal rearrangement and cell movement, apoptosis, and differentiation. With more than 500 gene products, the protein kinase family is one of the largest families of proteins in eukaryotes. The family has been classified in 8 major groups based on sequence comparison of their tyrosine (PTK) or serine/threonine (STK) kinase catalytic domains. The AGC kinase group consists of 63 kinases including the cyclic nucleotide-regulated protein kinase (PKA & PKG) family, the diacylglycerol-activated/phospholipid-dependent protein kinase C (PKC) family, the related to PKA and PKC (RAC/Akt) protein kinase family, the kinases that phosphorylate G protein-coupled receptors family (ARK), and the kinases that phosphorylate ribosomal protein S6 family (RSK).

Supplier: Thermo Scientific

Ephrin receptors and their ligands, the ephrins, mediate numerous developmental processes, particularly in the nervous system. Based on their structures and sequence relationships, ephrins are divided into the ephrin-A (EFNA) class, which are anchored to the membrane by a glycosylphosphatidylinositol linkage, and the ephrin-B (EFNB) class, which are transmembrane proteins. The Eph family of receptors are divided into 2 groups based on the similarity of their extracellular domain sequences and their affinities for binding ephrin-A and ephrin-B ligands. Ephrin receptors make up the largest subgroup of the receptor tyrosine kinase (RTK) family. The ligand-activated form of EphB2, which belongs to the Tyr family of protein kinases, interacts with multiple proteins, including GTPase-activating protein (RASGAP) through its SH2 domain. It binds RASGAP through the juxtamembrane tyrosines residues, and also interacts with PRKCABP and GRIP1 This type I membrane protein is expressed in brain, heart, lung, kidney, placenta, pancreas, liver and skeletal muscle. It is preferentially expressed in fetal brain. This protein contains putatively 2 fibronectin type III domains and 1 sterile alpha motif (SAM) domain.

Supplier: Bioss

PPM1D (Wip) is a serine/threonine phosphatase implicated in cell cycle control, spermatogenesis, and lymphoid cell function. The predicted 605-amino acid PPM1D protein contains 2 putative nuclear localization signals and 3 regions conserved in serine/threonine PP2C phosphatases, as well as characteristics of a type 2C phosphatase, including magnesium dependence and relative insensitivity to okadaic acid. PPM1D expression is induced in response to ionizing radiation in a p53-dependent manner. The accumulation of PPM1D mRNA following ionizing radiation is rapid and transient, and PPM1D protein is localized to the nucleus. PPM1D may contribute to growth inhibitory pathways activated in response to DNA damage in a p53-dependent manner. PPM1D inhibits phosphorylation of the p38 mitogen-activated (MAP)kinase protein. Through p38 MAPK, PPM1D modulates the CDKN2A tumor-suppressor locus. This gene is located in a chromosomal region known to be amplified in breast cancer, (located at 17q22-q23), is amplified in human breast tumor cell lines and in approximately 11% of primary breast tumors, and appears to lead to cell transformation by abrogating p53 tumor suppressor activity. Inactivation of the p38 MAPK through PPM1D overexpression resulting from PPM1D amplification may contributes to the development of human cancers by suppressing p53 activation. PPM1D null mice have increased susceptibility to pathogens and reduced male fertility and longevity.
Function : Required for the relief of p53-dependent checkpoint mediated cell cycle arrest. Binds to and dephosphorylates 'Ser-15' of TP53 and 'Ser-345' of CHEK1 which contributes to the functional inactivation of these proteins.
Subunit : Interacts with CHEK1 and CHEK2; dephosphorylates them.
Similarity : Belongs to the PP2C family. Contains 1 PP2C-like domain.

Supplier: Bioss

Serine/threonine-protein kinase that acts downstream of ERK (MAPK1/ERK2 and MAPK3/ERK1) signaling and mediates mitogenic and stress-induced activation of the transcription factors CREB1, ETV1/ER81 and NR4A1/NUR77, regulates translation through RPS6 and EIF4B phosphorylation, and mediates cellular proliferation, survival, and differentiation by modulating mTOR signaling and repressing pro-apoptotic function of BAD and DAPK1. In fibroblast, is required for EGF-stimulated phosphorylation of CREB1, which results in the subsequent transcriptional activation of several immediate-early genes. In response to mitogenic stimulation (EGF and PMA), phosphorylates and activates NR4A1/NUR77 and ETV1/ER81 transcription factors and the cofactor CREBBP. Upon insulin-derived signal, acts indirectly on the transcription regulation of several genes by phosphorylating GSK3B at 'Ser-9' and inhibiting its activity. Phosphorylates RPS6 in response to serum or EGF via an mTOR-independent mechanism and promotes translation initiation by facilitating assembly of the preinitiation complex. In response to insulin, phosphorylates EIF4B, enhancing EIF4B affinity for the EIF3 complex and stimulating cap-dependent translation. Is involved in the mTOR nutrient-sensing pathway by directly phosphorylating TSC2 at 'Ser-1798', which potently inhibits TSC2 ability to suppress mTOR signaling, and mediates phosphorylation of RPTOR, which regulates mTORC1 activity and may promote rapamycin-sensitive signaling independently of the PI3K/AKT pathway. Mediates cell survival by phosphorylating the pro-apoptotic proteins BAD and DAPK1 and suppressing their pro-apoptotic function. Promotes the survival of hepatic stellate cells by phosphorylating CEBPB in response to the hepatotoxin carbon tetrachloride (CCl4). Is involved in cell cycle regulation by phosphorylating the CDK inhibitor CDKN1B, which promotes CDKN1B association with 14-3-3 proteins and prevents its translocation to the nucleus and inhibition of G1 progression.

Supplier: Proteintech

Steroidogenic factor-1 (SF-1,STF-1), also known as NR5A1, regulates multiple genes involved in the adrenal and gonadal development and in the biosynthesis of a variety of hormones, including adrenal and gonadal steroids, anti-Mullerian hormone (AMH), and gonadotropins. SF-1 belongs to the fushi tarazu factor-1 (FTZ-F1) subfamily of orphan nuclear receptors. Initially identified as a tissue-specific transcriptional regulator of cytochrome P450 steroid hydroxylases, research studies of both global and tissue-specific knockout mice have demonstrated that SF-1 is required for the development of adrenal glands, gonads, ventromedial hypothalamus, and for the proper functioning of pituitary gonadotropes. Indeed, humans with mutations that render SF-1 transcriptionally inactive can present with testicular failure, ovarian failure, and adrenal insufficiency. Furthermore, dysregulation of SF-1 has been linked to diseases such as endometriosis and adrenocortical carcinoma.Like other nuclear hormone receptors, SF-1 has a modular domain structure composed of an N-terminal zinc finger DNA-binding domain, a ligand-binding domain, a C-terminal AF-2 activation domain, and a hinge region with AF-1-like activation activity. SF-1 also contains a fushi tarazu factor 1 box, which functions as an accessory DNA binding domain. SF-1 is primarily phosphorylated at Ser203, which is thought to enhance its transcriptional activity by promoting complex formation with transcriptional cofactors. In addition to phosphorylation at Ser203, SF-1 is subject to SUMO conjugation and acetylation at ε-amino groups of target lysine residues. Whereas SUMOylation represses SF-1 function, acetylation enhances its transcriptional activity.In the adult ovary, SF-1 localizes to theca/interstitial cells.