| URN | urn:agi-ProtModification:inout-urn:agi-llid:3643:out-urn:agi-llid:6464::positive:phosphorylation |
|---|---|
| References | 22 |
| Connectivity | 2 |
| Effect | positive |
| Mechanism | phosphorylation |
| Original # of References | 22 |
| TextRef | info:pmid/17222824#abs:1 |
|---|---|
| PubYear | 2007 |
| MedlineTA | Exp Cell Res |
| MedLine Reference | 17222824:0 |
| Sentence | Ligand-activated insulin receptor attracts and phosphorylates various substrates such as insulin receptor substrates 1-4 and Shc. |
| TextMods | 34: '(IR) ' -> '' 121: '(IRS) ' -> '' |
| TextRef | info:pmid/9932214#abs:6 |
|---|---|
| PubYear | 1998 |
| MedlineTA | Diabetes Metab |
| MedLine Reference | 9932214:5 |
| Sentence | Tyrosine phosphorylation of IRSs and Shc by the insulin receptor permits the activation of two major signalling pathways, the MAP kinase pathway and the Pl 3-kinase pathway. |
| TextRef | info:pmid/7651388#abs:1 |
|---|---|
| PubYear | 1995 |
| MedlineTA | Mol Cell Biol |
| MedLine Reference | 7651388:0 |
| Sentence | Insulin signals are mediated through tyrosine phosphorylation of specific proteins such as insulin receptor substrate 1 (IRS-1) and Shc by the activated insulin receptor . |
| TextMods | 170: '(IR)' -> '' |
| TextRef | info:pmid/8626723#abs:5 |
|---|---|
| PubYear | 1996 |
| MedlineTA | J Biol Chem |
| MedLine Reference | 8626723:4 |
| Sentence | Interestingly, this mutation completely abolished Shc phosphorylation by the insulin receptor in vivo whereas mutation of the arginine in the FLVRES motif of the Shc SH2 domain did not affect Shc phosphorylation by insulin. |
| TextMods | 77: 'IR ' -> 'insulin receptor ' |
| TextRef | info:pmid/7543044#abs:1 |
|---|---|
| PubYear | 1995 |
| MedlineTA | Endocrinology |
| MedLine Reference | 7543044:0 |
| Sentence | The insulin receptor phosphorylates insulin receptor substrate-1 (IRS-1) and Shc on tyrosine residues, both of which associate with the protein-abundant Src homology/growth factor receptor-bound protein 2 leading to p21ras activation. |
| TextMods | 204: '(ASH/GRB2) ' -> ' ' |
| TextRef | info:pmid/8969279#abs:5 |
|---|---|
| PubYear | 1996 |
| MedlineTA | Metabolism |
| MedLine Reference | 8969279:4 |
| Sentence | The inhibition of mitogenesis and AIB uptake was restored with the amelioration of the impaired tyrosine kinase activity and Shc phosphorylation by the introduction of abundant wild-type IGF-insulin receptor in Asp 1048 insulin receptor cells. |
| TextMods | 191: 'IR ' -> 'insulin receptor ' 220: 'IR ' -> 'insulin receptor ' |
| TextRef | info:pmid/9271396#abs:1 |
|---|---|
| PubYear | 1997 |
| MedlineTA | Mol Cell Biol |
| MedLine Reference | 9271396:0 |
| Sentence | The ability of insulin to stimulate protein synthesis and cellular growth is mediated through the insulin receptor , which phosphorylates Tyr residues in the insulin receptor substrate-signaling proteins (IRS-1 and IRS-2), Gab-1, and Shc. |
| TextMods | 115: '(IR)' -> '' |
| TextRef | info:pmid/11856336#body:65 |
|---|---|
| PubYear | 2002 |
| MedlineTA | Eur J Biochem |
| MedLine Reference | 11856336:1064 |
| Sentence | The activated insulin receptor phosphorylates tyrosine residues on insulin receptor substrate proteins, Shc, CAP and other intracellular substrates. |
| TextMods | 67: 'IRS ' -> 'insulin receptor substrate ' |
| TextRef | info:pmid/10517679#body:100 |
|---|---|
| PubYear | 1999 |
| MedlineTA | Mol Endocrinol |
| MedLine Reference | 10517679:1099 |
| Sentence | In the presence of insulin receptor subunit-1F18 or IRS-2, however, Shc bound to and was phosphorylated by the insulin receptor to the same degree as in their absence. |
| TextMods | 19: 'IRS' -> 'insulin receptor subunit' |
| TextRef | info:pmid/10194465#body:52 |
|---|---|
| PubYear | 1999 |
| MedlineTA | J Clin Invest |
| MedLine Reference | 10194465:1051 |
| Sentence | The phosphorylated insulin receptor binds and phosphorylates insulin receptor substrate proteins and Shc, which bind differentially to various downstream signaling proteins. |
| TextMods | 61: 'IRS ' -> 'insulin receptor substrate ' |
| TextRef | info:pmid/9837876#body:29 |
|---|---|
| PubYear | 1998 |
| MedlineTA | J Biol Chem |
| MedLine Reference | 9837876:1028 |
| Sentence | The activated insulin receptor phosphorylates endogenous substrate proteins, such as Shc and insulin receptor substrate (insulin receptor substrate)1 proteins (8-12). |
| TextMods | 121: 'IRS' -> 'insulin receptor substrate' |
| CellType | Adipocytes |
| TextRef | info:pmid/15878970#body:64 |
|---|---|
| PubYear | 2005 |
| MedlineTA | Endocrinology |
| MedLine Reference | 15878970:1063 |
| Sentence | The insulin receptor then phosphorylates substrates, e.g. the insulin receptor substrates and Shc that activate downstream signaling pathways to mediate the diverse effects of insulin (2). |
| CellLineName | GH4 |
| TextMods | 90: '(IRSs) ' -> '' |
| TextRef | info:pmid/15314154#body:35 |
|---|---|
| PubYear | 2004 |
| MedlineTA | Mol Cell Biol |
| MedLine Reference | 15314154:1034 |
| Sentence | Upon activation, Insulin receptor tyrosyl phosphorylates and activates multiple signaling molecules, including Insulin receptor substrate 1 (IRS1), IRS2, IRS3, IRS4, Shc, APS, and SH2-B (4, 27, 30, 40, 41, 43). |
| TextMods | 17: 'IR ' -> 'Insulin receptor ' 111: 'IR ' -> 'Insulin receptor ' |
| TextRef | info:pmid/15994203#body:59 |
|---|---|
| PubYear | 2005 |
| MedlineTA | Mol Endocrinol |
| MedLine Reference | 15994203:1058 |
| Sentence | The insulin receptor, on the other hand, is a receptor tyrosine kinase, which activates its signaling cascade by phosphorylating various intracellular substrates, including IRS-1, IRS-2, Shc, and Gαq/11. |
| CellType | Adipocytes |
| TextRef | info:pmid/10449437#body:78 |
|---|---|
| PubYear | 1999 |
| MedlineTA | J Clin Invest |
| MedLine Reference | 10449437:1077 |
| Sentence | Once bound and phosphorylated, insulin receptor will phosphorylate IRS-1, IRS-2, and Shc and activate phosphatidylinositol 3-kinase and Raf-mitogen-activated protein kinase pathways (1, 30). |
| TextMods | 31: 'IR ' -> 'insulin receptor ' 102: 'PI 3-kinase ' -> 'phosphatidylinositol 3-kinase ' 140: 'MAP ' -> 'mitogen-activated protein ' |
| Tissue | Muscle, Smooth, Vascular |
| CellType | Endothelial Cells |
| TextRef | info:pmid/19359342#body:56 |
|---|---|
| PubYear | 2009 |
| MedlineTA | Mol Endocrinol |
| MedLine Reference | 19359342:1055 |
| Sentence | Once autophosphorylated on critical tyrosine residues and activated, the insulin receptor (insulin receptors) phosphorylates intracellular substrates [insulin receptors substrates and Shc], that are the first effectors of the insulin signaling pathways (1). |
| TextMods | 91: 'IR' -> 'insulin receptors' 151: 'IR ' -> 'insulin receptors ' 180: '(IRS) ' -> '' |
| TextRef | info:pmid/11248703#body:239 |
|---|---|
| PubYear | 2001 |
| MedlineTA | Eur J Biochem |
| MedLine Reference | 11248703:1238 |
| Sentence | The activated insulin receptor kinase phosphorylates IRS-1 and Shc, which both associate with the adaptor proteins Grb-2-SOS, leading to p21ras, raf, MEK and mitogen-activated protein kinase activation. |
| TextMods | 14: 'IRK ' -> 'insulin receptor kinase ' 158: 'MAPK ' -> 'mitogen-activated protein kinase ' |
| CellType | Adipocytes |
| Organ | Liver |
| Organism | Rattus norvegicus |
| TextRef | info:pmid/11147799#body:46 |
|---|---|
| PubYear | 2001 |
| MedlineTA | Diabetes |
| MedLine Reference | 11147799:1045 |
| Sentence | Subsequently, the activated insulin receptor phosphorylates a number of protein substrates on tyrosine such as insulin receptor substrate -1/IRS-2 and Shc (4,5) which can then interact with multiple targets to mediate the pleiotropic actions of insulin (6,7,8). |
| TextMods | 28: 'IR ' -> 'insulin receptor ' 94: 'tyr ' -> 'tyrosine ' 138: '(IRS)' -> '' |
| TextRef | info:pmid/11607835#body:104 |
|---|---|
| PubYear | 2001 |
| MedlineTA | Oncogene |
| MedLine Reference | 11607835:1103 |
| Sentence | Interestingly, the p52Shc, but not the p46Shc, is efficiently phosphorylated by the insulin receptor and polyoma middle T antigen, both of which depend on phosphotyrosine-binding domain interactions; in contrast, the EGFR leads to efficient phosphorylation of both isoforms (Okada et al., 1995). |
| TextMods | 155: 'PTB ' -> 'phosphotyrosine-binding domain ' |
| TextRef | info:pmid/10903329#body:92 |
|---|---|
| PubYear | 2000 |
| MedlineTA | J Clin Invest |
| MedLine Reference | 10903329:1091 |
| Sentence | Once activated, the insulin receptor phosphorylates a number of important proximal substrates on tyrosine, including members of the insulin receptor substrate family (IRS1/2/3/4), the Shc adapter protein isoforms, SIRP family members, Gab-1, Cbl, and APS. |
| TextRef | info:pmid/9774456#body:41 |
|---|---|
| PubYear | 1998 |
| MedlineTA | J Biol Chem |
| MedLine Reference | 9774456:1040 |
| Sentence | Tyrosine phosphorylation of Shc by the insulin receptor initiates a major branch of the insulin signaling cascade; phosphorylated Shc binds Grb2, a small Src homology-2-containing adaptor molecule, leading to GDP/GTP exchange and activation of Ras through the guanine nucleotide exchange factor Sos (4). |
| TextRef | info:pmid/9415395#body:231 |
|---|---|
| PubYear | 1997 |
| MedlineTA | Mol Endocrinol |
| MedLine Reference | 9415395:1230 |
| Sentence | The activated insulin receptor kinase tyrosine phosphorylates IRS-1 (35, 36) and, in certain cell lines Shc (27, 36), each of which associates with Grb-2-Sos leading to the exchange of GDP for GTP on p21ras, resulting in p21ras activation and the sequential activation, by serine/threonine phosphorylation, of Raf and MEK. |
| TextMods | 14: 'IRK ' -> 'insulin receptor kinase ' |