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Insulin-Like Growth Factor IInsulin-Like Growth Factor IISomatomedinsInsulin-Like Growth Factor Binding ProteinsInsulin-Like Growth Factor Binding Protein 3Receptor, InsulinInsulin-Like Growth Factor Binding Protein 2Insulin-Like Growth Factor Binding Protein 5Insulin-Like Growth Factor Binding Protein 1Insulin-Like Growth Factor Binding Protein 4InsulinReceptor, IGF Type 1Insulin-Like Growth Factor Binding Protein 6Intercellular Signaling Peptides and ProteinsEpidermal Growth FactorCarrier ProteinsCells, CulturedSignal TransductionRNA, MessengerMolecular Sequence DataBase SequenceProtein BindingAmino Acid SequenceGrowth HormoneFollicular FluidCell DivisionSulfamethizoleGene Expression RegulationRecombinant ProteinsPregnancy-Associated Plasma Protein-ABinding SitesCell LineBlotting, WesternCell ProliferationPromoter Regions, GeneticGene ExpressionTumor Cells, CulturedReceptor, Epidermal Growth FactorEstradiolBlotting, NorthernTranscription FactorsCulture Media, ConditionedPoly(A)-Binding ProteinsDeciduaPhosphorylationCell Line, TumorImmunohistochemistryReceptors, SomatomedinDNATranscription, GeneticKineticsRadioimmunoassayBinding, CompetitiveVascular Endothelial Growth Factor AReverse Transcriptase Polymerase Chain ReactionCattleLiverDNA-Binding ProteinsGene Expression Regulation, NeoplasticTransforming Growth Factor betaOvarian FollicleFibroblast Growth Factor 2PregnancyDose-Response Relationship, DrugTime FactorsFibroblastsSequence Homology, Amino AcidGene Expression ProfilingApoptosisMolecular WeightTransfectionUp-RegulationPlatelet-Derived Growth FactorOligonucleotide Array Sequence AnalysisFibroblast Growth FactorsInsulin ResistanceBreast NeoplasmsProgesteroneSwineRats, Sprague-DawleyAmino AcidsCloning, MolecularIn Situ HybridizationNerve Growth FactorsGrowth SubstancesGranulosa CellsCase-Control StudiesTransforming Growth FactorsMutationDNA, ComplementaryTacrolimus Binding ProteinsGlucoseDNA PrimersRecombinant Fusion ProteinsHepatocyte Growth FactorGlycoproteinsEndothelial Growth FactorsTumor Necrosis Factor Decoy ReceptorsProtein Structure, TertiaryTumor Markers, Biological
AcidsIGFBPsIGF1High affinityReceptorsLinking the insulin receptorLigandHomologyPhosphorylationIGFBPCysteine-richProinsulinExtracellular signal-SecretionActivatesCDNASequenceConcentrationsEnzymatic activityPrecursorGRB2TyrosineMultifunctionalOxidativeAssaysResistanceGeneStructurallyBiologicalInhibitorNrf2CellsDeficiencyTransmembraneRecombinant humanModulateMetabolicGlucoseFamilyDiabetesAbnormalitiesInteractionCytokinesMitochondrialSerumProto-oncogeneSterileAbundantDependentAdultLipid
Acids7
IGFBPs5
  • Other IGFBPs bind to IGFI with a lower affinity and form complexes with shorter half-lives. (bmj.com)
  • IGFBPs modulate the biological activities of IGF proteins. (rndsystems.com)
  • Some IGFBPs may also have intrinsic bioactivity that is independent of their ability to bind IGF proteins. (rndsystems.com)
  • 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)
IGF17
  • The insulin-like peptides family is composed of insulin, insulin-like growth factor 1 (IGF1), and insulin-like growth factor (IGF2), together with IGF binding proteins (IGFBP1- IGFBP6) [ 1 ]. (scientificarchives.com)
  • Unlike IGF1 receptor (IGF1R) and insulin receptor (IR), IGF2R does not have intrinsic tyrosine kinase activity but can recruit G proteins, and even though these G-protein-activated pathways are not well characterized in the brain, PKC and phospholipase C are involved in IGF2 actions in the brain [ 6 ] and other cell types [ 7 ], respectively. (scientificarchives.com)
  • IGF2 can also bind, but with less affinity, to the IGF1 receptor (IGF1R) and the isoform A of the insulin receptor (IRA) [ 3 , 8 ], which may activate the signaling pathway downstream these tyrosine kinase receptors. (scientificarchives.com)
  • 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)
  • Hence, Insulin binds to IGF1R following the same mechanism and activated the intracellular pathways in the same way IGF1 does. (proteopedia.org)
  • Once IGF1 is bound to Insulin-like Growth Binding Protein (IGFBP), IGF-1 cannot be linked to IGF1R any longer. (proteopedia.org)
  • Insulin-like growth factor I (IGF1) belongs to the family of insulin-like growth factors that are structurally homologous to proinsulin. (joplink.net)
High affinity3
  • The IGFI receptor (IGFIR) can be found in most tissues of the body and binds IGFI with high affinity. (bmj.com)
  • The superfamily of insulin-like growth factor (IGF) binding proteins include the six high-affinity IGF binding proteins (IGFBP) and at least four additional low-affinity binding proteins referred to as IGFBP related proteins (IGFBP-rP). (rndsystems.com)
  • IGF2 binds with high affinity to the IGF2 receptor (IGF2R), which is also a mannose 6-phosphate (M6P) receptor. (scientificarchives.com)
Receptors2
Linking the insulin receptor1
  • 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)
Ligand4
  • The IGF2R binds M6P-containing ligand and IGF2 in two distinct sites [ 5 ]. (scientificarchives.com)
  • IGF-1 then acts as a ligand and can interact with Insulin Receptor protein and Insulin-like Growth Factor Binding Protein . (proteopedia.org)
  • Ligand-binding on α subunit induces activation of β subunit by autophosphorylation. (proteopedia.org)
  • Binds IGF-I in Western ligand blot. (eaglebio.com)
Homology4
  • 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)
  • Rat insulin-like growth factor binding protein-5 (IGFBP-5) is a 252 amino acid protein which preferentially binds IGF-II compared to IGF-I. It is highly conserved with a single amino acid difference [Asp187] compared to mouse IGFBP-5 [Glu187] and approximately 97% sequence homology to human IGFBP-5. (eaglebio.com)
  • Based on the amino acid sequence homology and biological activity in macrophages, Shimamoto et al ( 15 ) identified that HLP was identical to MSP ( 15 ). (spandidos-publications.com)
Phosphorylation4
  • Post-transitional modifications of IGFBP, including glycosylation, phosphorylation and proteolysis, have been shown to modify the affinities of the binding proteins to IGF. (rndsystems.com)
  • Hepatocyte growth factor (HGF) is produced by stromal and mesenchymal cells, and it stimulates epithelial cell proliferation, motility, morphogenesis and angiogenesis in various organs via tyrosine phosphorylation of its cognate receptor, Met. (spandidos-publications.com)
  • The enzymatic activity catalyzed by a tyrosine kinase is the transfer of the terminal phosphate from ATP to tyrosine residues on its substrates, a process known as protein tyrosine phosphorylation. (keralapharmacist.com)
  • Immunologic and confocal microscopic evidence also suggested a transient but significant stimulation of tyrosine phosphorylation of Cav-1 in β-cells briefly (for 15 min) exposed to IL-1β that was markedly attenuated by three structurally distinct inhibitors of protein tyrosine phosphorylation. (diabetesjournals.org)
IGFBP8
  • IGFI is a 70 amino acid polypeptide, and it circulates in the plasma bound to one of six IGF binding proteins (IGFBP). (bmj.com)
  • Production of IGFBP-3 and ALS proteins is also GH dependent. (bmj.com)
  • In direct ELISAs and Western blots, approximately 30% cross‑reactivity with recombinant mouse IGFBP-6 is observed, 5% cross‑reactivity with recombinant human (rh) IGFBP-2 is observed and less than 1% cross‑reactivity with rhIGFBP-1, rhIGFBP-3, rhIGFBP-4, and rhIGFBP-5 is observed. (rndsystems.com)
  • All IGFBP superfamily members are cysteine-rich proteins with conserved cysteine residues, which are clustered in the amino- and carboxy-terminal thirds of the molecule. (rndsystems.com)
  • Human IGFBP-6 cDNA encodes a 240 amino acid (aa) residue precursor protein with a putative 24 aa residue signal peptide that is processed to generate the 216 aa residue mature protein that is O-glycosylated. (rndsystems.com)
  • IGFBP-3 , the most abundant protein, accounts for 80% of all IGF binding. (proteopedia.org)
  • IGF-1 docks IGFBP with a series of polar and non-polar interactions all along its binding site. (proteopedia.org)
  • The Eagle Bioscience's Rat Insulin-like Growth Factor Binding Protein-5 (IGFBP-5) is for research use only and not to be used for diagnostic procedures. (eaglebio.com)
Cysteine-rich1
  • Keap1 is a cysteine-rich protein, known to be anchored to actin cytoskeleton [ 5 ], serving as an adaptor protein for the Cul3-dependent E3 ubiquitin ligase complex. (springer.com)
Proinsulin1
  • Proinsulin, insulin, and C-peptide concentrations in human portal and peripheral blood. (tsu.ge)
Extracellular signal-1
  • Insulin-induced activation of extracellular signal-regulated kinases [ERKs, also known as mitogen-activated protein (MAP) kinases] is mediated by Ras. (nih.gov)
Secretion2
  • Polonsky KS, Given BD, Van Cauter E. Twenty-four-hour profiles and pulsatile patterns of insulin secretion in normal and obese subjects. (tsu.ge)
  • Type 2 Diabetes Mellitus (T2DM) is a complex heterogeneous group of metabolic condition characterized by elevated levels of serum glucose, caused mainly by impairment in both insulin action and insulin secretion. (scialert.net)
Activates3
  • The activation of this pathway modulates gene transcription and activates multiple downstream Kinasesphosphatases branches, affecting key cellular processes such as protein synthesis, autophagy, apoptosis, and resistance to oxidative stress [ 9 ]. (scientificarchives.com)
  • Insulin activates Ras primarily by increasing the rate of guanine nucleotide-releasing activity. (nih.gov)
  • During the reviewing of articles in the Pubmed and Google Scholar database, the attention was attracted on the insulin-like growth factor system, which activates the cell growth and proliferation. (tsu.ge)
CDNA1
  • The human insulin receptor cDNA: the structural basis for hormone-activated transmembrane signalling. (tsu.ge)
Sequence3
  • R3 IGF-1 is an 83 amino acid analog of IGF-1 comprising the complete human IGF-1 sequence with the substitution of an Arg (R) for the Glu (E) at position three, hence R3, and a 13 amino acid extension peptide at the N terminus. (joplink.net)
  • The discovery of the antioxidant response element (ARE) have led to the conclusion that the battery of genes, including glutamate-cysteine ligase (GCL), thioredoxin reductase 1 (Txnrd1), NAD(P)H-quinone oxidoreductase 1 (NQO1) and heme oxygenase-1 (HMOX1) is regulated through Nrf2 binding to this consensus binding sequence [ 3 ]. (springer.com)
  • We further optimized the sequence to include hydrophilic asparagine (N) spacers (CPC +14N, (RRRR(NNRRR) 3 R) to minimize its competitive binding within the synovial fluid (SF) and enhance its cartilage targeting property (Fig. 1 A). (biomedcentral.com)
Concentrations3
  • Local production of IGFI in peripheral tissues makes up around 20% of circulating concentrations but stimulates growth in a paracrine fashion. (bmj.com)
  • Stimulates glucose transport in bone-derived osteoblastic (PyMS) cells and is effective at much lower concentrations than insulin, not only regarding glycogen and DNA synthesis but also with regard to enhancing glucose uptake. (joplink.net)
  • The dosage should not be based on growth hormone (GH) concentrations or signs and symptoms of acromegaly . (wikidoc.org)
Enzymatic activity1
Precursor1
  • Mature IGFs are generated by proteolytic processing of inactive precursor proteins, which contains the N- and C-terminal propeptide regions. (joplink.net)
GRB22
  • 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)
  • 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)
Tyrosine7
  • In response to insulin stimulation, this complex bound to tyrosine-phosphorylated IRS-1 (insulin receptor substrate-1) and Shc. (nih.gov)
  • Tyrosine-specific protein kinase activity is associated with the purified insulin receptor. (tsu.ge)
  • Like all tyrosine-kinase inhibitors, imatinib works by preventing a tyrosine kinase enzyme, in this case BCR-Abl, from phosphorylating subsequent proteins and initiating the signaling cascade necessary for cancer development, thus preventing the growth of cancer cells and leading to their death by apoptosis. (keralapharmacist.com)
  • One study demonstrated that imatinib mesylate was effective in patients with systemic mastocytosis, including those who had the D816V mutation in c-Kit.However, since imatinib binds to tyrosine kinases when they are in the inactive configuration and the D816V mutant of c-Kit is constitutively active, imatinib does not inhibit the kinase activity of the D816V mutant of c-Kit. (keralapharmacist.com)
  • Imatinib is a 2-phenyl amino pyrimidine derivative that functions as a specific inhibitor of a number of tyrosine kinase enzymes. (keralapharmacist.com)
  • The active sites of tyrosine kinases each have a binding site for ATP. (keralapharmacist.com)
  • Imatinib also inhibits the abl protein of non-cancer cells but cells normally have additional redundant tyrosine kinases which allow them to continue to function even if abl tyrosine kinase is inhibited. (keralapharmacist.com)
Multifunctional1
  • The multifunctional regulator nuclear factor erythroid 2-related factor (Nrf2) is considered not only as a cytoprotective factor regulating the expression of genes coding for anti-oxidant, anti-inflammatory and detoxifying proteins, but it is also a powerful modulator of species longevity. (springer.com)
Oxidative4
  • Furthermore, GSOs protected cells against GLU-induced apoptosis by reducing the expression of the mitochondrial apoptosis-associated Bcl-2 family effector proteins and protected cells from GLU-induced oxidative damage by increasing the nuclear translocation of Nrf2 and HO-1 expression. (sdbonline.org)
  • The autophagic pathway constitutively maintains cellular homeostasis by recycling cytoplasmic organelles and proteins, but it is also stimulated by environmental stress conditions, such as starvation, oxidative stress, and the accumulation of misfolded proteins. (mdpi.com)
  • Oxidative stress generated during such stressful conditions may damage DNA and proteins, and as a consequence the cellular processes are disturbed. (springer.com)
  • Single cells and organisms may adapt to harmful oxidative stress conditions, through stress-activated factors. (springer.com)
Assays2
  • SOMAVERT has significant structural similarity to growth hormone (GH) which causes it to cross-react in commercially available GH assays. (wikidoc.org)
  • Eagle Biosciences has quickly become a leading provider of ELISA assay kits, HPLC assay kits, Molecular Biology assays, antibodies, and proteins. (eaglebio.com)
Resistance4
  • Insulin-like growth factor system is activated during hyperinsulinemia, which alongside with insulin resistance and obesity forms basis for the development of metabolic syndrome. (tsu.ge)
  • Role of insulin resistance in human disease. (tsu.ge)
  • Replacement of GH in adults with GHD markedly reduces central obesity and substantially reduces total cholesterol levels but has produced little change in other risk factors, particularly insulin resistance and dyslipidemia. (medscape.com)
  • [ 13 ] For these patients, concerns are the persistent insulin resistance and dyslipidemia, together with the elevated plasma insulin and lipoprotein(a) levels observed with GH replacement. (medscape.com)
Gene4
  • Structure of the human insulin receptor gene and characterization of its promoter. (tsu.ge)
  • Various growth factors, cytokines, and prostaglandins upregulate HGF gene expression, including basic fibroblast growth factor, oncostatin M, hypoxia-inducible factor 1α and nuclear factor-κB (NF-κB) ( 9 ). (spandidos-publications.com)
  • By contrast, transforming growth factor (TGF)-β1 was demonstrated to markedly downregulate HGF gene expression ( 10 , 11 ). (spandidos-publications.com)
  • encoded by Nfe2l2 gene) is a transcription factor responsible for the regulation of cellular redox balance and protective antioxidant and phase II detoxification responses in mammals [ 1 , 2 ]. (springer.com)
Structurally1
  • The insulin-like growth factors, isolated from plasma, are structurally and functionally related to insulin but have a much higher growth-promoting activity. (joplink.net)
Biological1
  • It binds to extra-cellular matrix proteins which protect it from proteolysis and modify its biological functions. (eaglebio.com)
Inhibitor1
  • Nrf2 consists of six functional Neh domains (Neh1-Neh6), from which, the amino-terminal Neh2 domain controls binding Keap1-the inhibitor protein Kelch-like ECH-associated protein 1, that is responsible for the cytosolic sequestration of Nrf2 under physiological conditions (Fig. 2 a). (springer.com)
Nrf24
  • Levels of proteins, including Cyt C, Bcl-2/BAX, and Nrf2 /HO-1-associated proteins, were determined by western blotting and immunofluorescence. (sdbonline.org)
  • The major characteristics of Nrf2 are to some extent mimicked by Nrf2-dependent genes and their proteins including heme oxygenase-1 (HO-1), which besides removing toxic heme, produces biliverdin, iron ions and carbon monoxide. (springer.com)
  • This review summarizes our knowledge about Nrf2 and HO-1 across different phyla suggesting their conservative role as stress-protective and anti-aging factors. (springer.com)
  • Nrf2 is a master eukaryotic redox-active factor and belongs to Cap 'n' Collar (Cnc)-bZIP (basic leucine zipper) family of transcription factors. (springer.com)
Cells4
  • This protein is secreted in the beta cells of the Langerhans' islet in the pancreas and takes part in the glycogenesis. (proteopedia.org)
  • Skeletal muscle growth and regeneration involves the activity of resident adult stem cells, namely satellite cells (SC). (sdbonline.org)
  • HGF was cloned as a growth factor for hepatocytes ( 1 , 2 ), is identical to scatter factor (SF) and was originally discovered as a fibroblast-derived cell motility factor for epithelial cells ( 3 ). (spandidos-publications.com)
  • It is well established that inflammatory cytokines such as interleukin-1β (IL-1β) play a major regulatory role in the selective destruction of insulin-producing β-cells, resulting in the onset of type 1 diabetes ( 1 - 3 ). (diabetesjournals.org)
Deficiency5
  • Insulin-like growth factor 1 (IGFI) is produced in the liver and peripheral tissues including the growth plate, in response to growth hormone (GH) and is commonly used as a diagnostic marker of growth hormone deficiency (GHD) and to monitor GH replacement therapy, as recommended by an international GH consensus. (bmj.com)
  • Hyposomatotropism is a deficiency in the release of pituitary growth hormone (somatotropin), resulting in short stature. (medscape.com)
  • Patients with growth hormone deficiency (GHD) typically have hyperlipidemia, increased body fat, premature atherosclerotic plaques, delayed bone maturation, and impaired cardiac function. (medscape.com)
  • The diagnosis of growth hormone (GH) deficiency (GHD), or hyposomatotropism, remains controversial. (medscape.com)
  • The mitochondrial genes associated with cytochrome c oxidase deficiency provide instructions for making proteins that are part of a large enzyme group (complex) called cytochrome c oxidase (also known as complex IV). (medlineplus.gov)
Transmembrane1
  • Insulin-like Growth Factor 1 Receptor ( IGF-1R ) is a transmembrane protein receptor. (proteopedia.org)
Recombinant human1
Modulate1
  • T2DM is a complex trait where common genetic variants having modest individual effects act together and interact with environmental factors to modulate the risk of the disease. (scialert.net)
Metabolic1
  • The metabolic syndrome: prevalence and associated risk factor findings in the US population from the Third National Health and Nutrition Examination Survey, 1988-1994. (tsu.ge)
Glucose1
  • May be a physiological regulator of [1-14C]-2-deoxy-D-glucose (2DG) transport and glycogen synthesis in osteoblasts. (joplink.net)
Family3
  • IGF2 is the less characterized member of this family, and in mice and rats its expression in the brain occurs during embryonic development and adulthood but declines during aging [ 2 ]. (scientificarchives.com)
  • Insulin-like Growth Factor ( IGF-1 ) is a member of the insulin protein family. (proteopedia.org)
  • HGF forms a family with HGF-like protein (HLP), a unique protein with a domain structure similar to that of HGF ( 12 ). (spandidos-publications.com)
Diabetes1
  • The aim of this review was to discuss the current understanding of Type 2 Diabetes Mellitus (T2DM) genetic advance and aetiology. (scialert.net)
Abnormalities1
  • Transaminase elevations normalized with time, most often after suspending treatment (SOMAVERT should be used in accordance with the information presented in Table 2 with respect to liver test abnormalities while on Somavert treatment). (wikidoc.org)
Interaction1
  • The T2DM is a genetically heterogeneous disease, with several relatively rare monogenic forms and a number of more common forms resulting from a complex interaction of genetic and environmental factors. (scialert.net)
Cytokines1
  • OA onset results in the upregulation of several inflammatory cytokines including interleukin 1 (IL-1) and tumor necrosis factor-alpha (TNF-α) which in turn upregulate the expression of proteolytic enzymes that break down the cartilage matrix [ 3 , 4 ]. (biomedcentral.com)
Mitochondrial1
  • Changes in mitochondrial DNA are among the best-studied genetic factors associated with age-related hearing loss. (medlineplus.gov)
Serum1
  • Macrophage stimulating protein (MSP) was discovered as a serum protein that promoted mouse macrophage motility ( 13 ), and was later purified to homogeneity from human plasma ( 14 ). (spandidos-publications.com)
Proto-oncogene1
Sterile1
  • 1 month, 2 to 8 °C under sterile conditions after reconstitution. (rndsystems.com)
Abundant1
  • RACK1 was expressed transiently in the skeletal muscle of post-natal mice, being abundant in the early phase of muscle growth and almost disappearing in adult mature fibers. (sdbonline.org)
Dependent2
  • Administration of recombinant IGF2 also enhanced memory retention and prevented forgetting, processes that were dependent on the binding of IGF2 to its receptor [ 11 ]. (scientificarchives.com)
  • Vantaggiato C, Formentini I, Bondanza A, Bonini C, Naldini L, Brambilla R. ERK1 and ERK2 mitogen-activated protein kinases affect Ras-dependent cell signaling differentially. (tsu.ge)
Adult2
  • Collectively, this study provides the first evidence that transient levels of the evolutionarily conserved factor RACK1 are critical for adult SC activation and proper skeletal muscle regeneration, favoring the efficient progression of SC from a committed to a fully differentiated state. (sdbonline.org)
  • Achievement of final adult height consistent with a child's genetic potential remains the primary therapeutic endpoint for recombinanat human growth hormone (rhGH) therapy in the pediatric population. (medscape.com)
Lipid1
  • In the present study, we examined potential contributory roles of membrane-associated, cholesterol-enriched lipid rafts/caveolae and their constituent proteins (e.g., caveolin-1 [Cav-1]) as potential sites for IL-1β−induced nitric oxide (NO) release in the isolated β-cell. (diabetesjournals.org)