| URN | urn:agi-ProtModification:inout-urn:agi-llid:5770:out-urn:agi-llid:3643::negative:dephosphorylation |
|---|---|
| References | 55 |
| Connectivity | 2 |
| Effect | negative |
| Mechanism | dephosphorylation |
| Original # of References | 55 |
| TextRef | info:pmid/7487920#abs:3 |
|---|---|
| PubYear | 1995 |
| MedlineTA | Biochem J |
| MedLine Reference | 7487920:2 |
| Sentence | Compound 12 competitively inhibited insulin-receptor dephosphorylation by PTP-1B. |
| TextRef | info:pmid/19029027#abs:13 |
|---|---|
| PubYear | 2009 |
| MedlineTA | Invest Ophthalmol Vis Sci |
| MedLine Reference | 19029027:12 |
| Sentence | In vitro, PTP1B is able to dephosphorylate the autophosphorylated insulin receptor. |
| TextMods | 66: 'IR' -> 'insulin receptor' |
| Organ | Retina |
| TextRef | info:pmid/15269244#abs:2 |
|---|---|
| PubYear | 2004 |
| MedlineTA | J Biochem |
| MedLine Reference | 15269244:1 |
| Sentence | However, it remains unclear where PTP1B dephosphorylates insulin receptor and inhibits its activity. |
| TextRef | info:pmid/11936837#abs:2 |
|---|---|
| PubYear | 2002 |
| MedlineTA | Mol Cell Biochem |
| MedLine Reference | 11936837:1 |
| Sentence | Phosphotyrosine phosphatase 1B (PTP1B) dephosphorylates phosphotyrosine residues present on the insulin receptor . |
| TextMods | 72: '(pTyr) ' -> '' 113: '(IR)' -> '' |
| TextRef | info:pmid/17634210#abs:1 |
|---|---|
| PubYear | 2007 |
| MedlineTA | Clin Chem |
| MedLine Reference | 17634210:0 |
| Sentence | Protein tyrosine phosphatase 1B (PTPN1) dephosphorylates insulin receptors and attenuates insulin signaling. |
| TextRef | info:pmid/12237455#abs:5 |
|---|---|
| PubYear | 2002 |
| MedlineTA | Protein Sci |
| MedLine Reference | 12237455:4 |
| Sentence | On SPOT membranes, insulin receptor peptides with phosphotyrosine 1163 were efficiently bound by PTP1B D181A, and dephosphorylated by PTP-1B. |
| TextMods | 19: 'IR ' -> 'insulin receptor ' |
| TextRef | info:pmid/11401301#abs:2 |
|---|---|
| PubYear | 2001 |
| MedlineTA | Anal Biochem |
| MedLine Reference | 11401301:1 |
| Sentence | PTP1B has been implicated in the negative regulation of the insulin signaling pathway by dephosphorylating the activated insulin receptor. |
| TextRef | info:pmid/11579209#abs:1 |
|---|---|
| PubYear | 2001 |
| MedlineTA | Mol Endocrinol |
| MedLine Reference | 11579209:0 |
| Sentence | PTP1B is a protein tyrosine phosphatase that negatively regulates insulin sensitivity by dephosphorylating the insulin receptor. |
| TextRef | info:pmid/15504985#abs:2 |
|---|---|
| PubYear | 2004 |
| MedlineTA | Diabetes |
| MedLine Reference | 15504985:1 |
| Sentence | PTP-1B has been implicated in negatively regulating insulin signaling by dephosphorylating the phosphotyrosine residues of the insulin receptor. |
| TextRef | info:pmid/12504077#abs:2 |
|---|---|
| PubYear | 2003 |
| MedlineTA | Biochem Biophys Res Commun |
| MedLine Reference | 12504077:1 |
| Sentence | PTP1B dephosphorylates the insulin receptor and insulin receptor substrates (IRS-1/2), inhibiting the insulin-signaling pathway. |
| TextRef | info:pmid/15997237#abs:1 |
|---|---|
| PubYear | 2005 |
| MedlineTA | Br J Pharmacol |
| MedLine Reference | 15997237:0 |
| Sentence | Protein tyrosine phosphatase 1B (PTP1B) acts as a physiological negative regulator of insulin signaling by dephosphorylating the activated insulin receptor . |
| TextMods | 156: '(IR)' -> '' |
| TextRef | info:pmid/15924436#abs:5 |
|---|---|
| PubYear | 2005 |
| MedlineTA | Biochemistry |
| MedLine Reference | 15924436:4 |
| Sentence | However, chromium did not inhibit recombinant human PTP1B using either p-nitrophenyl phosphate or the tyrosine-phosphorylated insulin receptor as the substrate. |
| TextRef | info:pmid/17545163#abs:2 |
|---|---|
| PubYear | 2007 |
| MedlineTA | J Biol Chem |
| MedLine Reference | 17545163:1 |
| Sentence | Protein-tyrosine phosphatase 1B (PTP1B) dephosphorylates tyrosine residues in insulin receptor and possibly insulin receptor substrate proteins, thereby inhibiting insulin signaling. |
| TextMods | 78: 'IR ' -> 'insulin receptor ' 108: 'IRS ' -> 'insulin receptor substrate ' |
| TextRef | info:pmid/15733745#abs:11 |
|---|---|
| PubYear | 2005 |
| MedlineTA | Biochimie |
| MedLine Reference | 15733745:10 |
| Sentence | These results strongly suggest that PTP1B not only dephosphorylates the insulin receptor that has been activated by insulin, but also regulates the insulin receptor precursor during its biosynthesis. |
| TextRef | info:pmid/11163213#abs:1 |
|---|---|
| PubYear | 2000 |
| MedlineTA | Mol Cell |
| MedLine Reference | 11163213:0 |
| Sentence | The protein tyrosine phosphatase PTP1B is responsible for negatively regulating insulin signaling by dephosphorylating the phosphotyrosine residues of the insulin receptor kinase activation segment. |
| TextMods | 179: '(IRK) ' -> '' |
| TextRef | info:pmid/9890920#abs:2 |
|---|---|
| PubYear | 1999 |
| MedlineTA | Biochemistry |
| MedLine Reference | 9890920:1 |
| Sentence | Protein tyrosine phosphatases PTP1B and PTPalpha are known to dephosphorylate the insulin receptor and may contribute to insulin resistance in diseases such as diabetes. |
| TextMods | 30: '(PTPases) ' -> '' |
| TextRef | info:pmid/11960490#abs:2 |
|---|---|
| PubYear | 2002 |
| MedlineTA | J Med Chem |
| MedLine Reference | 11960490:1 |
| Sentence | PTP1B negatively regulates insulin signaling, in part, by dephosphorylating key tyrosine residues within the regulatory domain of the beta-subunit of the insulin receptor, thereby attenuating receptor kinase activity. |
| TextRef | info:pmid/16363874#abs:1 |
|---|---|
| PubYear | 2006 |
| MedlineTA | J Biomol Struct Dyn |
| MedLine Reference | 16363874:0 |
| Sentence | Protein Tyrosine Phosphatase 1B (PTP1B) has been shown to be a negative regulator of insulin signaling by dephosphorylating key tyrosine residues within the regulatory domain of the beta-subunit of the insulin receptor. |
| TextRef | info:pmid/10751417#abs:1 |
|---|---|
| PubYear | 2000 |
| MedlineTA | J Biol Chem |
| MedLine Reference | 10751417:0 |
| Sentence | Previous studies suggested that protein-tyrosine phosphatase 1B (PTP1B) antagonizes insulin action by catalyzing dephosphorylation of the insulin receptor and/or other key proteins in the insulin signaling pathway. |
| TextMods | 155: '(IR) ' -> '' |
| TextRef | info:pmid/11341829#abs:5 |
|---|---|
| PubYear | 2001 |
| MedlineTA | Biochemistry |
| MedLine Reference | 11341829:4 |
| Sentence | These inhibitors disrupted the binding of PTP1B to activated insulin receptors in vitro and prevented the loss of tyrosine kinase (IRTK) activity that accompanied PTP1B-catalyzed dephosphorylation of insulin receptors. |
| TextMods | 61: 'IR ' -> 'insulin receptors ' 200: 'IR' -> 'insulin receptors' |
| TextRef | info:pmid/15135305#abs:6 |
|---|---|
| PubYear | 2004 |
| MedlineTA | Biochem Pharmacol |
| MedLine Reference | 15135305:5 |
| Sentence | In an indirect stimulation of the insulin receptor, metformin inhibited endogenous tyrosine phosphatases and purified human protein tyrosine phosphatase 1B that dephosphorylate and inhibit the insulin receptor kinase. |
| CellType | Oocytes |
| Organism | Xenopus laevis |
| TextRef | info:pmid/11806712#abs:1 |
|---|---|
| PubYear | 2002 |
| MedlineTA | J Med Chem |
| MedLine Reference | 11806712:0 |
| Sentence | Protein tyrosine phosphatase 1B (PTP1B) negatively regulates insulin signaling in part by dephosphorylating key tyrosine residues within the regulatory domain of the beta-subunit of the insulin receptor , thereby attenuating receptor tyrosine kinase activity. |
| TextMods | 203: '(IR)' -> '' |
| TextRef | info:pmid/11223182#abs:2 |
|---|---|
| PubYear | 2001 |
| MedlineTA | Mol Cell Endocrinol |
| MedLine Reference | 11223182:1 |
| Sentence | Because protein tyrosine phosphatase 1B (PTP1B) binds and subsequently dephosphorylates insulin receptors, inhibitors of PTP1B-insulin receptors binding are potential insulin 'sensitizers.' A Scintillation Proximity Assay was developed to characterize and quantitate PTP1B-insulin receptors binding. |
| TextMods | 88: 'IR' -> 'insulin receptors' 127: 'IR ' -> 'insulin receptors ' 279: 'IR ' -> 'insulin receptors ' 222: '(SPA) ' -> '' |
| TextRef | info:pmid/15632081#body:175 |
|---|---|
| PubYear | 2005 |
| MedlineTA | Mol Cell Biol |
| MedLine Reference | 15632081:1174 |
| Sentence | Regulation of insulin receptor phosphorylation by PTP1B and TCPTP. |
| TextMods | 14: 'IR ' -> 'insulin receptor ' |
| CellType | B-Lymphocytes |
| TextRef | info:pmid/17481567#title:1 |
|---|---|
| PubYear | 2007 |
| MedLine Reference | 17481567:100 |
| Sentence | An enzyme-linked immunosorbent assay to measure insulin receptor dephosphorylation by PTP1B. |
| TextRef | info:pmid/11970889#body:146 |
|---|---|
| PubYear | 2002 |
| MedlineTA | Dev Cell |
| MedLine Reference | 11970889:1145 |
| Sentence | PTP1B may dephosphorylate the insulin receptor by the same mechanism, but this remains to be demonstrated. |
| TextRef | info:pmid/12424235#body:49 |
|---|---|
| PubYear | 2003 |
| MedlineTA | J Biol Chem |
| MedLine Reference | 12424235:1048 |
| Sentence | Multiple studies indicated that PTP1B dephosphorylates the EGFR (16, 17) and the insulin receptor (14, 33-35). |
| TextMods | 98: '(IR) ' -> '' |
| TextRef | info:pmid/14966267#body:251 |
|---|---|
| PubYear | 2004 |
| MedlineTA | Mol Cell Biol |
| MedLine Reference | 14966267:1250 |
| Sentence | Role of Nox4 in the modulation of insulin receptor tyrosine phosphorylation by PTP1B. |
| CellType | Adipocytes |
| TextRef | info:pmid/15082519#body:618 |
|---|---|
| PubYear | 2004 |
| MedlineTA | Endocr Rev |
| MedLine Reference | 15082519:1617 |
| Sentence | Furthermore, PTP1B associates only with activated receptors and can dephosphorylate both the insulin receptor and IRS proteins. |
| TextMods | 93: 'IR ' -> 'insulin receptor ' |
| TextRef | info:pmid/9443918#body:89 |
|---|---|
| PubYear | 1998 |
| MedlineTA | Curr Biol |
| MedLine Reference | 9443918:1088 |
| Sentence | PTP1B dephosphorylates the insulin receptor and insulin receptor substrates (IRS-1/2), inhibiting the insulin-signaling pathway. |
| TextRef | info:pmid/17562854#body:363 |
|---|---|
| PubYear | 2007 |
| MedlineTA | Mol Cell Biol |
| MedLine Reference | 17562854:1362 |
| Sentence | Dephosphorylation of the Insr by PTP-1B is thought to occur following receptor internalization into endosomes (3). |
| Organ | Liver |
| TextRef | info:pmid/18006633#body:326 |
|---|---|
| PubYear | 2008 |
| MedlineTA | Endocrinology |
| MedLine Reference | 18006633:1325 |
| Sentence | PTP1B is induced to associate with insulin receptor by insulin and to dephosphorylate insulin receptor on specific tyrosine residues (30, 31). |
| TextMods | 35: 'IR ' -> 'insulin receptor ' 86: 'IR ' -> 'insulin receptor ' |
| TextRef | info:pmid/11856336#body:182 |
|---|---|
| PubYear | 2002 |
| MedlineTA | Eur J Biochem |
| MedLine Reference | 11856336:1181 |
| Sentence | Indeed, crystal structure and kinetic studies provide evidence that PTP-1B preferentially dephosphorylates tyrosines 1150 and 1151 of the insulin receptor [90]. |
| TextMods | 138: 'IR ' -> 'insulin receptor ' |
| TextRef | info:pmid/12649327#body:56 |
|---|---|
| PubYear | 2003 |
| MedlineTA | Mol Endocrinol |
| MedLine Reference | 12649327:1055 |
| Sentence | PTP1B is thought to negatively regulate insulin signaling by dephosphorylating the insulin receptor as well as its substrates IRS-1 and IRS-2 (2, 3, 4). |
| TextMods | 100: '(IR) ' -> '' |
| TextRef | info:pmid/14693698#body:178 |
|---|---|
| PubYear | 2004 |
| MedlineTA | Diabetes |
| MedLine Reference | 14693698:1177 |
| Sentence | Ptp1b normally inhibits insulin signaling by dephosphorylating the insulin receptor as it passes by the endoplasmic reticulum during recycling (15). |
| CellType | Insulin-Secreting Cells |
| TextRef | info:pmid/11726652#body:255 |
|---|---|
| PubYear | 2002 |
| MedlineTA | J Biol Chem |
| MedLine Reference | 11726652:1254 |
| Sentence | However, in the presence of GST-Grb14, insulin receptor dephosphorylation by PTP1B was decreased by 47% compared with 72% in the presence of GST (Fig. 7 A, lanes 5 and 6). |
| TextMods | 39: 'IR ' -> 'insulin receptor ' |
| Organ | Ovary |
| Organism | Mesocricetus auratus |
| TextRef | info:pmid/11248703#body:217 |
|---|---|
| PubYear | 2001 |
| MedlineTA | Eur J Biochem |
| MedLine Reference | 11248703:1216 |
| Sentence | Indeed, PTP1B directly interacts with the activated insulin receptor [47] and dephosphorylates the activated insulin receptor as well as downstream insulin effectors [48,49]. |
| CellLineName | 293T |
| TextRef | info:pmid/11147799#body:54 |
|---|---|
| PubYear | 2001 |
| MedlineTA | Diabetes |
| MedLine Reference | 11147799:1053 |
| Sentence | PTP1B has been demonstrated to dephosphorylate the insulin receptor and IRS-1 as well as associate with the tyrosine phosphorylated insulin receptor (21,22). |
| TextMods | 51: 'IR ' -> 'insulin receptor ' 108: 'tyr ' -> 'tyrosine ' 132: 'IR ' -> 'insulin receptor ' |
| CellType | Oocytes |
| Organism | Xenopus laevis |
| TextRef | info:pmid/16249458#body:64 |
|---|---|
| PubYear | 2005 |
| MedlineTA | Diabetes |
| MedLine Reference | 16249458:1063 |
| Sentence | Activated insulin receptor and receptor substrate-1 are dephosphorylated by PTP-1B (2), and phosphorylated JAK2 and STAT3 have been identified as its targets in the leptin pathway (3,4). |
| TextRef | info:pmid/11872675#body:338 |
|---|---|
| PubYear | 2002 |
| MedlineTA | Diabetes |
| MedLine Reference | 11872675:1337 |
| Sentence | Among them, PTP1B has been shown extensively to be expressed in insulin-sensitive tissues and also to bind to and dephosphorylate insulin receptor (44-46) and more recently IRS-1 (30). |
| TextMods | 130: 'IR ' -> 'insulin receptor ' |
| CellType | Adipocytes |
| TextRef | info:pmid/17259385#body:66 |
|---|---|
| PubYear | 2007 |
| MedlineTA | Diabetes |
| MedLine Reference | 17259385:1065 |
| Sentence | Protein-tyrosine phosphatase 1B acts as a physiological negative regulator of insulin signaling by dephosphorylating the phosphotyrosine residues of the insulin receptor and IRS-1 (14,15). |
| TextMods | 29: '(PTP)' -> '' |
| CellType | Muscle Fibers, Skeletal |
| TextRef | info:pmid/16093451#body:295 |
|---|---|
| PubYear | 2005 |
| MedlineTA | J Am Soc Nephrol |
| MedLine Reference | 16093451:1294 |
| Sentence | protein tyrosine phosphatase 1B has an impact on insulin and cytokine signaling by dephosphorylating the insulin receptor and interfering with the phosphorylation status of membrane-bound receptors (43). |
| TextMods | 0: 'PTP1B ' -> 'protein tyrosine phosphatase 1B ' |
| TextRef | info:pmid/11970898#body:257 |
|---|---|
| PubYear | 2002 |
| MedlineTA | Dev Cell |
| MedLine Reference | 11970898:1256 |
| Sentence | In muscle and liver (and possibly other tissues), PTP1B negatively regulates insulin signaling by directly dephosphorylating the insulin receptor (Elchebly et al., 1999). |
| TextMods | 129: 'IR ' -> 'insulin receptor ' |
| Tissue | Muscles |
| Organ | Liver |
| TextRef | info:pmid/12612081#body:47 |
|---|---|
| PubYear | 2003 |
| MedlineTA | Mol Cell Biol |
| MedLine Reference | 12612081:1046 |
| Sentence | PTP1B can dephosphorylate the insulin receptor in vitro, and with substrate-trapping mutants, several studies have demonstrated that PTP1B can recognize the insulin receptor as a cellular substrate (reviewed in reference 51). |
| TextMods | 30: 'IR ' -> 'insulin receptor ' 157: 'IR ' -> 'insulin receptor ' |
| TextRef | info:pmid/18806091#body:172 |
|---|---|
| PubYear | 2008 |
| MedlineTA | J Nutr |
| MedLine Reference | 18806091:1171 |
| Sentence | It has also been suggested that chromium can attenuate the concentrations of protein tyrosine phosphatase 1B, which dephosphorylates the insulin receptor and functions as a negative regulator of insulin signaling (27). |
| CellType | Adipocytes |
| TextRef | info:pmid/12907755#body:44 |
|---|---|
| PubYear | 2003 |
| MedlineTA | Mol Endocrinol |
| MedLine Reference | 12907755:1043 |
| Sentence | The best-known example of a Protein tyrosine phosphatase that inhibits receptor activity is PTP1B, which has phosphorylated insulin receptor as a substrate (11), and also negatively regulates leptin receptor signaling (12, 13, 14, 15). |
| TextMods | 28: 'PTP ' -> 'Protein tyrosine phosphatase ' |
| TextRef | info:pmid/12949365#body:50 |
|---|---|
| PubYear | 2003 |
| MedlineTA | J Nutr |
| MedLine Reference | 12949365:1049 |
| Sentence | Furthermore, the higher insulin receptor activation in muscle of the neonate is associated with reduced activity of protein tyrosine phosphatase-1B (PTP-1B), which functions to dephosphorylate the activated insulin receptor (15). |
| TextMods | 24: 'IR ' -> 'insulin receptor ' 207: 'IR ' -> 'insulin receptor ' |
| Tissue | Muscles |
| TextRef | info:pmid/14749734#body:217 |
|---|---|
| PubYear | 2004 |
| MedlineTA | EMBO J |
| MedLine Reference | 14749734:1216 |
| Sentence | Dephosphorylation of the insulin receptor by PTP1b is thought to occur following receptor internalization into endosomes, which occurs 30 s to 1 min following insulin treatment (Burgess et al, 1992; Asante-Appiah and Kennedy, 2003). |
| TextMods | 25: 'IR ' -> 'insulin receptor ' |
| CellType | Hepatocytes |
| TextRef | info:pmid/16522684#body:238 |
|---|---|
| PubYear | 2006 |
| MedlineTA | J Cell Sci |
| MedLine Reference | 16522684:1237 |
| Sentence | PTP1B has been shown to dephosphorylate several cell surface receptor tyrosine kinases, including the insulin receptor , epidermal growth factor receptor (EGFR) and platelet-derived growth factor receptor (Tonks, 2003[Go]). |
| TextMods | 119: '(IR)' -> '' 205: '(PDGFR) ' -> '' |
| Organ | Ground substance |
| TextRef | info:pmid/15561934#body:50 |
|---|---|
| PubYear | 2004 |
| MedlineTA | Diabetes |
| MedLine Reference | 15561934:1049 |
| Sentence | Overexpression studies have shown that PTP-1B dephosphorylates the insulin receptor in vitro, as well as induces the downregulation of insulin receptor substrate-1 (IRS-1) and insulin-stimulated phosphatidylinositol 3-kinase activity (3-6). |
| TextMods | 225: '(PI3-K) ' -> '' |
| Organ | Liver |
| TextRef | info:pmid/16505227#body:71 |
|---|---|
| PubYear | 2006 |
| MedlineTA | Diabetes |
| MedLine Reference | 16505227:1070 |
| Sentence | PTP1B is a ubiquitously expressed tyrosine phosphatase, playing an important role in the negative regulation of insulin signaling by dephosphorylating the insulin receptor tyrosine kinase, reducing its kinase activity, and thus inhibiting insulin signaling (8). |
| TextRef | info:pmid/17525361#body:135 |
|---|---|
| PubYear | 2007 |
| MedlineTA | Endocr Rev |
| MedLine Reference | 17525361:1134 |
| Sentence | Protein tyrosine phosphatases (e.g., PTP1B) that dephosphorylate the insulin receptor and IRS-1 and lipid phosphatases (e.g., SHIP-2 and PTEN) that dephosphorylate PI(3,4,5)P3 play important roles in negative regulation of insulin-signaling pathways (17). |
| TextMods | 69: 'IR ' -> 'insulin receptor ' |
| TextRef | info:pmid/16931767#body:300 |
|---|---|
| PubYear | 2007 |
| MedlineTA | Endocr Rev |
| MedLine Reference | 16931767:1299 |
| Sentence | PTP-1B can dephosphorylate both IGF-insulin receptor (63) and IRS-1 (64), and, indeed, in mouse embryonic fibroblasts derived from PTP-1B-deficient mice, IGF-I-induced IGF-insulin receptor autophosphorylation and kinase activity were higher than in controls (63). |
| TextMods | 36: 'IR ' -> 'insulin receptor ' 90: 'MEFs ' -> 'mouse embryonic fibroblasts ' 172: 'IR ' -> 'insulin receptor ' |
| CellType | Fibroblasts |
| TextRef | info:pmid/15611135#body:75 |
|---|---|
| PubYear | 2005 |
| MedlineTA | J Biol Chem |
| MedLine Reference | 15611135:1074 |
| Sentence | The insulin receptor is activated by phosphorylation of 2 adjacent tyrosine residues (1162 and 1163), and structural analysis of the PTP1B catalytic domain (18) has revealed that PTP1B possess two phosphotyrosine binding sites that are required for PTP1B to bind and dephosphorylate the insulin receptor efficiently. |
| TextRef | info:pmid/19017730#body:63 |
|---|---|
| PubYear | 2009 |
| MedlineTA | Am J Physiol Endocrinol Metab |
| MedLine Reference | 19017730:1062 |
| Sentence | Initial work focused on PTP1B as a regulator of insulin signaling, since it was shown that PTP1B directly dephosphorylates and inhibits signaling from the insulin receptor (11, 33, 36) in a variety of peripheral tissues (8, 14, 15, 41) and that whole body PTP1B deletion increases insulin sensitivity and protects against diet-induced obesity and insulin resistance (16, 20). |