• Tyrosine phosphorylation of IRS-1 by insulin receptor (IR) introduces multiple binding sites for proteins bearing SH2 homology domain, such as PI3K, Grb-2/Sos complex and SHP2. (wikipedia.org)
  • Tyrosine phosphorylation of the insulin receptors or IGF-1 receptors, upon extracellular ligand binding, induces the cytoplasmic binding of IRS-1 to these receptors, through its PTB domains. (wikipedia.org)
  • An alternative multi-site phosphorylation of Serine/Threonine in IRS-1 regulates insulin signaling positively and negatively. (wikipedia.org)
  • C-terminal region contains most of the phosphorylation sites of the protein. (wikipedia.org)
  • It has been shown that TNFα causes insulin resistance and multi-site S/T phosphorylation, which results in block of interaction between IRS-1 and juxtamembrane domain peptide, thus converting IRS-1 into an inactive state. (wikipedia.org)
  • Different Serine phosphorylation of IRS-1, caused by various molecules, such as fatty acids, TNFα and AMPK, has different effects on the protein, but most of these effects include cellular re-localization, conformational and steric changes. (wikipedia.org)
  • These processes lead to decrease in Tyrosine phosphorylation by insulin receptors and diminished PI3K recruitment. (wikipedia.org)
  • SOCS proteins act by binding to IR and by interfering with IR phosphorylation of IRS-1, therefore attenuating insulin signaling. (wikipedia.org)
  • They can also bind to JAK, causing a subsequent decrease in IRS-1 tyrosine phosphorylation. (wikipedia.org)
  • Concomitant activation of the insulin-like growth factor-1 receptor, Akt, and extracellular signal-regulated protein kinase 1 and 2 as well as increased phosphorylation of Bad also were unique to the hippocampus of APP Sw mice. (jneurosci.org)
  • In addition, the increased expression of transthyretin and insulin-like growth factor-2 and the increased phosphorylation of Bad in hippocampal neurons were maintained in 12-month-old APP Sw mice when compared with age-matched controls. (jneurosci.org)
  • CREB phosphorylation involved c-Src-dependent extracellular signal-regulated kinase 1/2 activation, but not protein kinase A, protein kinase C, or calmodulin-dependent kinase II, and occurred also in cells transfected with AR or estrogen receptor mutants that do not localize into the nucleus. (unical.it)
  • Expression of the mutants differentially affected insulin-induced phosphorylation of IRS1, AKT, ERK, and STAT3. (scielo.br)
  • The intact receptor lacks tyrosine kinase activity, but binding of GH and dimerization results in association with JAK2, a member of the Janus kinase family, which results in self-phosphorylation of the JAK2 and a cascade of phosphorylation of cellular proteins. (medscape.com)
  • 2004) Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. (scielo.br)
  • 2005) Activating mutations in the tyrosine kinase domain of the epidermal growth factor receptor are associated with improved survival in gefitinib-treated chemorefractory lung adenocarcinomas. (scielo.br)
  • In contrast to the activated epidermal growth factor receptor that binds the GRB2-Sos complex directly, activation of the insulin receptor results in the interaction of GRB2-Sos with IRS-1 and Shc, thus linking the insulin receptor to Ras signaling pathways. (nih.gov)
  • IRS-1 integrates signalling from insulin receptor (InsR), insulin-like growth factor-1 receptor (IGF1R) and many other cytokine receptors and is elevated in β-catenin induced cells. (wikipedia.org)
  • The IRS proteins function as adaptors and transmit signals from multiple receptors. (scielo.br)
  • In addition to binding to the insulin receptor, IRS1 also binds to and transmits signals from the receptors of prolactin, growth hormone (GH), leptin, vascular endothelial growth factor (VEGF), tropomyosin receptor kinase B (TrkB), anaplastic lymphoma kinase (ALK), insulin like growth factor (IGF1), and integrins ( Vuori and Ruoslathi , 1994 Vuori K and Ruoslahti E (1994) Association of insulin receptor substrate-1 with integrins. (scielo.br)
  • IGF-1 binds to both insulin and IGF-1 receptors to stimulate PI3K/Akt activity ( 25 ). (amegroups.org)
  • IGF-1, IGF-2 and Insulin can interact with one another of the different receptors. (proteopedia.org)
  • IGF binding involves 3 basic types of receptors: the structurally homologous insulin receptor and type 1 IGF receptor and the distinctive type 2 IGF-II/mannose-6-phosphate receptor. (medscape.com)
  • In addition to these receptors, hybrid receptors consisting of a dimer from the IGF-I receptor paired with the insulin receptor, are ubiquitous and the respective expression of these receptors varies from tissue to tissue. (medscape.com)
  • The HH pathway regulates growth of small cell lung Protopanaxdiol IC50 cancer (SCLC) and non-small cell lung tumor (NSCLC) (6 15 HH pathway people are abundantly indicated within the premalignant and malignant lungs of cyclin E-expressing transgenic mice (16). (acancerjourney.info)
  • We now show that, in prostate cancer cells, stimulation with either androgens or estrogens up-regulates IGF-IR by inducing cyclic AMP response element-binding protein (CREB) activation. (unical.it)
  • Metz H, Busch SE, Hanke ML, Kargl J, Kim KH and Houghton M (2014) Insulin receptor substrate-1 regulates immune cell content in lung adenocarcinoma. (scielo.br)
  • Therefore, the various concentration of the insulin proteins regulates the cell activity in different context, for instance in excess of glucose or lack of Growth Hormone. (proteopedia.org)
  • Insulin receptor substrate 1 plays a key role in transmitting signals from the insulin receptor (IR) and insulin-like growth factor 1 receptor (IGF-1) to intracellular pathways PI3K / Akt and Erk MAP kinase pathways. (wikipedia.org)
  • This enables IRS-1 to activate several signalling pathways, including the PI3K pathway and the MAP kinase pathway. (wikipedia.org)
  • Upon binding of insulin to the insulin receptor (IR), IRS1 is phosphorylated at several YXXM motifs creating docking sites for the binding of PI3Kp85, which activates AKT kinase. (scielo.br)
  • Metz HE and Houghton AM (2011) Insulin receptor substrate regulation of phosphoinositide 3-kinase. (scielo.br)
  • Hence, Insulin binds to IGF1R following the same mechanism and activated the intracellular pathways in the same way IGF1 does. (proteopedia.org)
  • Activates the MAPK signaling pathway and induces cell migration. (cusabio.com)
  • Insulin activates Ras primarily by increasing the rate of guanine nucleotide-releasing activity. (nih.gov)
  • Hedgehog (HH) signaling is essential in development and carcinogenesis because it controls cell fate and proliferation (1 2 Three mammalian HH ligands [sonic (sHH) desert and indian] are lipid-modified secreted proteins (1 2 The HH receptor Patched 1 (Ptch1) inhibits this pathway by locking Smoothened (Smo) in an inactive conformation. (acancerjourney.info)
  • Cyclopamine a naturally-occurring HH antagonist binds to Smo and inhibits HH signaling (14). (acancerjourney.info)
  • MDM2 binds to and inhibits TP53 activity. (medscape.com)
  • Formation of the Grb-2/Sos complex, also known as the RAS guanine nucleotide exchange factor complex, results in ERK1/2 activation. (wikipedia.org)
  • Piperine significantly increased the ratio of phospho-AKT1 (pAKT1)/AKT1, phosphos-AKT2 (pAKT2)/AKT2, and phospho-ERK1/2 (pERK1/2)/ERK1/2 in the testis. (frontiersin.org)
  • ERK1/2 and AKT pathways may involve in the piperine-mediated stimulation of Leydig cell development. (frontiersin.org)
  • In addition, insulin can also increase IGF-1 (insulin-growth factor -1) by inhibiting production of IGFBPs 1, 2 and 3 (insulin-like growth factor binding proteins) ( 25 ). (amegroups.org)
  • IGF binding proteins ( IGFBPs ) weight 24 to 45 kDa. (proteopedia.org)
  • All six IGFBPs share 50% homology with each other and have binding affinities at the same order of magnitude for IGF-1 and IGF-2 but have greater affinities then IGF1 for its receptor. (proteopedia.org)
  • Hepatic IGF-I circulates almost entirely bound to IGF binding proteins (IGFBPs), with less than 1% being free. (medscape.com)
  • The IGFBPs are a family of 6 structurally related proteins with a high affinity for binding IGF. (medscape.com)
  • Thus, even a small insulin-like effect of IGF-I could be more important than that of insulin itself, were it not for the IGFBPs that control the availability and activity of IGF-I. In fact, intravenous infusion of recombinant human IGF-I (rhIGF-I) can induce hypoglycemia, especially in the IGFBP3 deficient state. (medscape.com)
  • Insulin receptor substrate 1 (IRS-1) is a signaling adapter protein that in humans is encoded by the IRS1 gene. (wikipedia.org)
  • Sesti G, Federici M, Hribal ML, Lauro D, Sbraccia P and Lauro R (2001) Defects of the insulin receptor substrate (IRS) system in human metabolic disorders. (scielo.br)
  • Ma Z, Gibson SL, Byrne MA, Zhang J, White MF and Shaw LM (2006) Suppression of insulin receptor substrate 1 (IRS-1) promotes mammary tumor metastasis. (scielo.br)
  • In response to insulin stimulation, this complex bound to tyrosine-phosphorylated IRS-1 (insulin receptor substrate-1) and Shc. (nih.gov)
  • Basal manifestation of these varieties in tumor cells was hypothesized to point growth dependence of the cells for the HH pathway. (acancerjourney.info)
  • Multiple Smo inhibitors had been researched in lung tumor as the HH pathway can be energetic in subsets of the malignancies. (acancerjourney.info)
  • Cyclin E-driven transgenic and transplantable murine lung tumor versions that spontaneously triggered the HH pathway had been available for research as was a combined human being normal-malignant lung cells array Protopanaxdiol IC50 with an connected clinical data source. (acancerjourney.info)
  • The presented results implicate usage of Smo inhibitors for lung along with other cancers whenever a gene profile indicative of HH pathway dependence can be expressed within Protopanaxdiol IC50 the tumor cells. (acancerjourney.info)
  • Asthma, which is not dependent on type 2 immunity (and often steroid-resistant), may be related to airway neutrophilia, increased tumor necrosis factor (TNF) alpha, and therefore to Th17 responses. (biomedcentral.com)
  • We previously found that bladder tumor growth was significantly reduced in rats treated with BI-TK + GCV after 15 days of treatment [ 10 ]. (biomedcentral.com)
  • [ 1 ] His prediction was subsequently supported by the cloning of the retinoblastoma tumor suppressor gene ( RB1 ) and by functional studies of the retinoblastoma protein, Rb. (medscape.com)
  • Like Rb protein, many of the proteins encoded by tumor suppressor genes act at specific points in the cell cycle. (medscape.com)
  • Other inhibitory pathways include SOCS proteins and O-GlcNAcylation of IRS-1. (wikipedia.org)
  • IRS-1 plays important biological function for both metabolic and mitogenic (growth promoting) pathways: mice deficient of IRS1 have only a mild diabetic phenotype, but a pronounced growth impairment, i.e. (wikipedia.org)
  • The IRS proteins (IRS1-4) are the family of adaptors regulating metabolic and mitogenic signaling pathways ( Hanke and Mann , 2009 Hanke S and Mann M (2009) The phosphotyrosine interactome of the insulin receptor family and its substrates IRS-1 and IRS-2. (scielo.br)
  • Insulin-induced activation of extracellular signal-regulated kinases [ERKs, also known as mitogen-activated protein (MAP) kinases] is mediated by Ras. (nih.gov)
  • In the pituitary gland inside the brain, Growth Hormone ( GH ) is secreted and its release enable transcription of IGF1 in liver and depending on the nutritional state, a paracrine or autocrine activation IGF-1 occurs. (proteopedia.org)
  • Once IGF1 is bound to Insulin-like Growth Binding Protein (IGFBP), IGF-1 cannot be linked to IGF1R any longer. (proteopedia.org)
  • Therefore, increases in serum levels of this IGFBP result in a decrease of IGF1 activity thus inhibiting the cellular pathways. (proteopedia.org)
  • Recent research demonstrated that the homology between IGF-1R and the insulin receptor (IR) subunits allow them to bind and form a functionnal hybrid IR/IGF-1R receptor. (proteopedia.org)
  • Here, we show that insulin-induced activation of ERKs was enhanced by stable overexpression of growth factor receptor-bound protein 2 (GRB2) but not by overexpression of GRB2 proteins with point mutations in the Src homology 2 and 3 domains. (nih.gov)
  • However, BF + GCV only induced apoptosis via Fas/FasL signal pathway accompanied with increased P53 expression. (biomedcentral.com)
  • As the activation of PI3K/Akt signal pathway increases the resistance of several cancer cell lines such ovarian, lung cancer to chemotherapeutic drugs ( 7 , 8 ), it is possible that PI3K/Akt may also play a role in the poor prognosis of obesity-associated colon cancer. (amegroups.org)
  • Ligand-binding on α subunit induces activation of β subunit by autophosphorylation. (proteopedia.org)
  • A hallmark of the predominant asthma subtype is the stimulation of the adaptive immune system [ 2 ], specifically a Th2-type response, with involvement of interleukin (IL)-4 and IL-13, as well as antigen-specific immunoglobulin (Ig) type E. Type 2 innate immunity typically involves type 2 innate lymphoid cells, especially in older patients. (biomedcentral.com)
  • We mapped all estrogen receptor and RNA polymerase II binding sites on a genome-wide scale, identifying the authentic cis binding sites and target genes, in breast cancer cells. (nature.com)
  • The expression of transthyretin, a protein shown to sequester Aβ and prevent amyloid fibril formation in vitro , and several genes in the insulin-signaling pathway, e.g., insulin-like growth factor-2, were increased selectively in the hippocampus of APP Sw mice. (jneurosci.org)
  • The most overexpressed genes included Fc Fragment of IgG Binding Protein ( FCGBP , logFC = 3.01, pFDR = 0.015), Mucin 2 ( MUC2 , logFC = 2.78, pFDR = 0.015), and Alpha 1B Defensin ( DEFA1B , logFC = 2.73, pFDR = 0.024). (biomedcentral.com)
  • Abstract Insulin-like growth factor-I receptor (IGF-IR) overexpression may play a role in prostate cancer progression. (unical.it)
  • GRB2 overexpression led to increased formation of a complex between the guanine nucleotide-releasing factor Sos (the product of the mammalian homolog of son of sevenless gene) and GRB2. (nih.gov)
  • Repression of HH pathway people Cells SOS2 had been independently treated using the Smo inhibitors: cyclopamine SANT-1 and MK-4101. (acancerjourney.info)
  • We found previously that, in prostate cancer cells, IGF-IR is up-regulated by both androgens and estrogens via a nongenotropic pathway. (unical.it)
  • This study tested insulin-caused resistance to oxaliplatin via activation of PI3K/Akt pathway in HT29 cells. (amegroups.org)
  • Insulin decreased drug efficacy of oxaliplatin in HT29 cells, which could be mediated by the activation of the PI3K/Akt pathway. (amegroups.org)
  • This protein is secreted in the beta cells of the Langerhans' islet in the pancreas and takes part in the glycogenesis. (proteopedia.org)
  • Moreover, a dominant negative form of Ras (with Ser17 substituted with Asn) blocked insulin-induced activation of ERKs in cells that overexpressed GRB2. (nih.gov)
  • Activating the HH pathway affects expression of Ptch1 cyclin D1 cyclin E insulin-like growth factor 2 (IGF2) insulin-like growth factor binding protein 6 (IGFBP6) GILZ and other species (2-5). (acancerjourney.info)
  • A decrease of IGFBP6 expression can involve a decrease in the expression of N-cadherin and transcription factor Slug. (cusabio.com)
  • IGFBP6 might be an important regulator and prognostic factor for glioma. (cusabio.com)
  • Results suggest that insulin like growth factor binding protein 6 (IGFBP6) may be an independent prognostic biomarker for nasopharyngeal carcinoma (NPC). (cusabio.com)
  • We identified a novel SNP variant, Chr12:g.53494591T>C. c.T430C (p.S144P) in the insulin-like growth factor binding protein-6 (IGFBP6) gene. (cusabio.com)
  • PI3K specific inhibitor Ly294002 abolished such an effect of insulin. (amegroups.org)
  • Many altered factors in obesity are known to activate PI3K/Akt pathway including increased blood levels of insulin, Insulin-like growth factor-1, leptin, IL-6, IL-17, TNF-α and decreased blood level of adiponectin ( 9 , 10 ). (amegroups.org)
  • Thus, it is possible that these factors can activate PI3K/Akt pathway which in turn increases the resistance to chemotherapy in obesityassociated colon cancer ( 11 ). (amegroups.org)
  • Insulin can stimulate PI3K/Akt activity to increase the carcinogenesis of colon cancer ( 9 ). (amegroups.org)
  • The activation of PI3K/Akt pathway can increase cell survival, cell growth and proliferation ( 22-24 ). (amegroups.org)
  • IGF-1 then acts as a ligand and can interact with Insulin Receptor protein and Insulin-like Growth Factor Binding Protein . (proteopedia.org)
  • Altogether, these mechanisms stimulate IRS-1 degradation and insulin resistance. (wikipedia.org)
  • IGF-binding proteins prolong the half-life of the IGFs and have been shown to either inhibit or stimulate the growth promoting effects of the IGFs on cell culture. (cusabio.com)
  • Description: A sandwich quantitative ELISA assay kit for detection of Human Pappalysin 2 (PAPPA2) in samples from tissue homogenates, cell lysates or other biological fluids. (signetlabs.com)
  • Description: This is Double-antibody Sandwich Enzyme-linked immunosorbent assay for detection of Human Pappalysin 2 (PAPPA2) in serum, plasma and other biological fluids. (signetlabs.com)
  • Description: Enzyme-linked immunosorbent assay based on the Double-antibody Sandwich method for detection of Human Pappalysin 2 (PAPPA2) in samples from Serum, plasma and other biological fluids with no significant corss-reactivity with analogues from other species. (signetlabs.com)
  • Description: Quantitative sandwich ELISA for measuring Human Pappalysin-2 (PAPPA2) in samples from cell culture supernatants, serum, whole blood, plasma and other biological fluids. (signetlabs.com)
  • Description: A sandwich ELISA kit for detection of Pappalysin 2 from Human in samples from blood, serum, plasma, cell culture fluid and other biological fluids. (signetlabs.com)
  • Description: This is Double-antibody Sandwich Chemiluminescent immunoassay for detection of Human Pappalysin 2 (PAPPA2) in serum, plasma and other biological fluids. (signetlabs.com)
  • The discovery that a variety of tissues can express vitamin D receptor (VDR) has opened new ways of research related to vitamin D biological effects and molecular pathways [ 1 - 3 ]. (hindawi.com)
  • It also opens a new way of thinking for biomedical scientists, whether RNA modification will be another important factor to regulate the biological development of neoplastic diseases. (biomedcentral.com)
  • During insulin resistance induced by hyperglycemia, glucose accumulates in tissues as its hexosamine metabolite UDP-GlcNAc. (wikipedia.org)
  • IGF-I deficiency can be the result of GH resistance or insensitivity due to genetic disorders of the GH receptor causing GH receptor deficiency (growth hormone receptor deficiency [GHRD], Laron syndrome) or postreceptor defects, including the principal transduction agent STAT5b, the IGF-I/IGFBP3 stabilizer acid labile subunit (ALS), the IGF-I gene, or the IGF-I receptor. (medscape.com)
  • Figure 1: Summary of estrogen receptor and RNA PolII binding sites and correlation with nucleotide and gene number. (nature.com)
  • Figure 3: Estrogen receptor and RNA PolII binding relative to specific gene targets. (nature.com)
  • In the version of this article initially published online, the estrogen receptor and RNA PolII binding data were aligned incorrectly in the top panel of Figure 3, which represents estrogen receptor binding at the ESR1 gene region. (nature.com)
  • The most critical of these proteins is the signal transducer and activator of transcription 5b (STAT5b), which couples GH binding to the activation of gene expression that leads to the intracellular effects of GH, including synthesis of IGF-I, insulin-like growth factor binding protein 3 (IGFBP3), and ALS. (medscape.com)
  • For example, the TP53 gene, located on chromosome 17, encodes a 53-kd nuclear protein that functions as a cell cycle checkpoint. (medscape.com)
  • A recent prospective study further demonstrated that fasting blood level of insulin is positively correlated with waist circumference and colon cancer ( 18 ). (amegroups.org)
  • The apoptosis was transduced by multiple signaling pathways mediated by FasL and TNFR2 and mainly activated the mitochondrial control of apoptosis via Bid and Bim, which was rescued by silencing Bid or/and Bim . (biomedcentral.com)
  • In this data source Ptch1 and Smo sequences had been available with information regarding manifestation of varieties connected with HH pathway activation. (acancerjourney.info)
  • It further leads to activation of the Akt and mTor pathways inside the cell. (proteopedia.org)
  • Figure 4: Identification of enriched motifs within the estrogen receptor binding sites and validation of transcription factor binding. (nature.com)
  • As a transcription factor whose expression is increased by DNA damage, p53 blocks cell division at the G1 phase of the cell cycle to allow DNA repair. (medscape.com)
  • The CDK4-cyclinD complex normally phosphorylates the retinoblastoma protein (Rb protein), leading to release of the E2F transcription factor and cell cycle progression. (medscape.com)
  • HH pathway deregulation occurs in many tumors including lung (6) breast (7) and pancreatic (8) cancers. (acancerjourney.info)
  • An important development in cancer research over the past 2 decades has been the recognition that genetic changes drive the pathogenesis of tumors of both adulthood and childhood. (medscape.com)
  • [ 2 ] Targeted disruption of TP53 in the mouse leads to the development of various tumors (see image below). (medscape.com)
  • The coding RNA of this protein creates 4 isoforms differing from each other due to RNA splicing. (proteopedia.org)
  • Consistent with increase in serum T, piperine increased Leydig cell number, cell size, and multiple steroidogenic pathway proteins, including steroidogenic acute regulatory protein, cholesterol side-chain cleavage enzyme, 3β-hydroxysteroid dehydrogenase 1, 17α-hydroxylase/20-lyase, and steroidogenic factor 1 expression levels. (frontiersin.org)
  • Figure 7: Assessment of estrogen receptor binding properties in different cell systems. (nature.com)
  • [1] . It is the main actor in primary growth cell control. (proteopedia.org)
  • The GH molecule binds to its specific cell surface receptor (GHR), which dimerizes with another GHR molecule so that the single GH molecule is enveloped by 2 GHR molecules. (medscape.com)
  • The p19ARF protein, which is encoded by the same locus as p16, also leads to cell cycle arrest by inhibiting the ability of MDM2 to inactivate TP53. (medscape.com)
  • The p16INK4A protein is a cell-cycle inhibitor that acts by inhibiting activated cyclin D:CDK4/6 complexes, which play a crucial role in the control of the cell cycle by phosphorylating Rb protein. (medscape.com)
  • Briefly, they contain the human APP 695 with the double mutation K670N and M671L (Swedish mutation) and are driven by the prion protein promoter. (jneurosci.org)
  • We also showed that CREB binds to IGF-IR promoter region and identified the relevant CREB-binding site at the 5'-untranslated region fragment of IGF-IR promoter. (unical.it)
  • DNA damage increases TP53 levels through an ATM-dependent pathway. (medscape.com)
  • Epidemiological studies showed that obesity is associated with many cancers including colon cancer ( 2 ). (amegroups.org)
  • Increased insulin in obesity may play a key role in obesity-associated carcinogenesis and prognosis of colon cancer ( 12 ). (amegroups.org)
  • However, the effect of insulin has not been studied in colon cancer prognosis although increased insulin level has been regarded as a major factor for the poor prognosis of obesity-associated breast cancer and reduction of insulin by metformin was found to improve treatment outcome ( 26 , 27 ). (amegroups.org)
  • Tg2576 mice overexpress a mutant form of human amyloid precursor protein with the Swedish mutation (APP Sw ), resulting in high β-amyloid (Aβ) levels in the brain. (jneurosci.org)
  • Direct evidence linking the INK4A locus to tumorigenesis was provided by the targeted disruption of exon 2 of INK4A in mice. (medscape.com)
  • Following insulin binding, the insulin receptor (IR) autophosphorylates itself and creates docking sites for IRS proteins. (scielo.br)