| http://purl.uniprot.org/citations/16055440 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/16055440 | http://www.w3.org/2000/01/rdf-schema#comment | "The function of insulin receptor substrate-1 (IRS-1), a key molecule of insulin signaling, is modulated by phosphorylation at multiple serine/threonine residues. Phorbol ester stimulation of cells induces phosphorylation of two inhibitory serine residues in IRS-1, i.e. Ser-307 and Ser-318, suggesting that both sites may be targets of protein kinase C (PKC) isoforms. However, in an in vitro system using a broad spectrum of PKC isoforms (alpha, beta1, beta2, delta, epsilon, eta, mu), we detected only Ser-318, but not Ser-307 phosphorylation, suggesting that phorbol ester-induced phosphorylation of this site in intact cells requires additional signaling elements and serine kinases that link PKC activation to Ser-307 phosphorylation. As we have observed recently that the tyrosine phosphatase Shp2, a negative regulator of insulin signaling, is a substrate of PKC, we studied the role of Shp2 in this context. We found that phorbol ester-induced Ser-307 phosphorylation is reduced markedly in Shp2-deficient mouse embryonic fibroblasts (Shp2-/-) whereas Ser-318 phosphorylation is unaltered. The Ser-307 phosphorylation was rescued by transfection of mouse embryonic fibroblasts with wild-type Shp2 or with a phosphatase-inactive Shp2 mutant, respectively. In this cell model, tumor necrosis factor-alpha-induced Ser-307 phosphorylation as well depended on the presence of Shp2. Furthermore, Shp2-dependent phorbol ester effects on Ser-307 were blocked by wortmannin, rapamycin, and the c-Jun NH2-terminal kinase (JNK) inhibitor SP600125. This suggests an involvement of the phosphatidylinositol 3-kinase/mammalian target of rapamycin cascade and of JNK in this signaling pathway resulting in IRS-1 Ser-307 phosphorylation. Because the activation of these kinases does not depend on Shp2, it is concluded that the function of Shp2 is to direct these activated kinases to IRS-1."xsd:string |
| http://purl.uniprot.org/citations/16055440 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m506549200"xsd:string |
| http://purl.uniprot.org/citations/16055440 | http://purl.uniprot.org/core/author | "Beck A."xsd:string |
| http://purl.uniprot.org/citations/16055440 | http://purl.uniprot.org/core/author | "Fiedler H."xsd:string |
| http://purl.uniprot.org/citations/16055440 | http://purl.uniprot.org/core/author | "Kellerer M."xsd:string |
| http://purl.uniprot.org/citations/16055440 | http://purl.uniprot.org/core/author | "Haring H.U."xsd:string |
| http://purl.uniprot.org/citations/16055440 | http://purl.uniprot.org/core/author | "Staiger H."xsd:string |
| http://purl.uniprot.org/citations/16055440 | http://purl.uniprot.org/core/author | "Moeschel K."xsd:string |
| http://purl.uniprot.org/citations/16055440 | http://purl.uniprot.org/core/author | "Mussig K."xsd:string |
| http://purl.uniprot.org/citations/16055440 | http://purl.uniprot.org/core/date | "2005"xsd:gYear |
| http://purl.uniprot.org/citations/16055440 | http://purl.uniprot.org/core/name | "J Biol Chem"xsd:string |
| http://purl.uniprot.org/citations/16055440 | http://purl.uniprot.org/core/pages | "32693-32699"xsd:string |
| http://purl.uniprot.org/citations/16055440 | http://purl.uniprot.org/core/title | "Shp2 is required for protein kinase C-dependent phosphorylation of serine 307 in insulin receptor substrate-1."xsd:string |
| http://purl.uniprot.org/citations/16055440 | http://purl.uniprot.org/core/volume | "280"xsd:string |
| http://purl.uniprot.org/citations/16055440 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/16055440 |
| http://purl.uniprot.org/citations/16055440 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/16055440 |
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| http://purl.uniprot.org/uniprot/#_Q63848-mappedCitation-16055440 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/16055440 |
| http://purl.uniprot.org/uniprot/#_Q05C78-mappedCitation-16055440 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/16055440 |
| http://purl.uniprot.org/uniprot/#_Q4VA93-mappedCitation-16055440 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/16055440 |
| http://purl.uniprot.org/uniprot/#_P20444-mappedCitation-16055440 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/16055440 |
| http://purl.uniprot.org/uniprot/#_P35235-mappedCitation-16055440 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/16055440 |
| http://purl.uniprot.org/uniprot/#_Q810H1-mappedCitation-16055440 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/16055440 |