Mechanism of Tyrosine Phosphorylation and Activation of Phospholipase C-γ1
| Autor: | Sue Goo Rhee, Fujio Sekiya, Yeun Ju Kim, Benoit Poulin |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
inorganic chemicals
biology Phospholipase C Chemistry Kinase Tyrosine phosphorylation macromolecular substances Cell Biology Protein tyrosine phosphatase environment and public health Biochemistry Molecular biology Dephosphorylation enzymes and coenzymes (carbohydrates) chemistry.chemical_compound biology.protein bacteria Phosphorylation Protein phosphorylation Molecular Biology Platelet-derived growth factor receptor |
| Zdroj: | Journal of Biological Chemistry. 279:32181-32190 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m405116200 |
| Popis: | Phospholipase C-gamma 1 (PLC-gamma 1) is phosphorylated on three tyrosine residues: Tyr-771, Tyr-783, and Tyr-1253. With the use of antibodies specific for each of these phosphorylation sites, we have now determined the kinetics and magnitude of phosphorylation at each site. Phosphorylation of Tyr-783, which is essential for lipase activation, was observed in all stimulated cell types examined. The extent of phosphorylation of Tyr-1253 was approximately 50 to 70% of that of Tyr-783 in cells stimulated with platelet-derived growth factor (PDGF) or epidermal growth factor (EGF), but Tyr-1253 phosphorylation was not detected in B or T cell lines stimulated through B- and T-cell antigen receptors, respectively. Tyr-771 was phosphorylated only at a low level in all cells studied. In cells stimulated with PDGF, phosphorylation and dephosphorylation of Tyr-783 and of Tyr-1253 occurred with similar kinetics; the receptor kinase appeared to phosphorylate both sites, albeit with Tyr-783 favored over Tyr-1253, before the bound PLC-gamma 1 was released, and phosphorylation at the two sites occurred independently. PDGF and EGF induced similar levels of phosphorylation of Tyr-783 and of Tyr-1253 in a cell line that expressed receptors for both growth factors. However, only PDGF, not EGF, elicited substantial PLC activity, suggesting that Tyr-783 phosphorylation was not sufficient for enzyme activation. Finally, concurrent production of phosphatidylinositol 3,4,5-trisphosphate was found to contribute to the activation of phosphorylated PLC-gamma 1. |
| Databáze: | OpenAIRE |
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