The platelet-derived growth factor receptor stimulation of p42/p44 mitogen-activated protein kinase in airway smooth muscle involves a G-protein-mediated tyrosine phosphorylation of Gab1
| Autor: | Nigel J. Pyne, Soma Rakhit, Susan Pyne |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
MAPK/ERK pathway
Dynamins endocrine system G protein Guinea Pigs GAB1 Biology GTP-Binding Protein alpha Subunits Gi-Go environment and public health GTP Phosphohydrolases chemistry.chemical_compound Phosphatidylinositol 3-Kinases Growth factor receptor GTP-Binding Proteins Animals Receptors Platelet-Derived Growth Factor Phosphorylation Protein kinase A Cells Cultured Pharmacology Mitogen-Activated Protein Kinase 1 Tyrosine phosphorylation Muscle Smooth Phosphoproteins Molecular biology Cell biology Enzyme Activation enzymes and coenzymes (carbohydrates) chemistry biology.protein Insulin Receptor Substrate Proteins Molecular Medicine Tyrosine biological phenomena cell phenomena and immunity hormones hormone substitutes and hormone antagonists Platelet-derived growth factor receptor |
| Zdroj: | Molecular pharmacology. 58(2) |
| ISSN: | 0026-895X |
| Popis: | Using cultured airway smooth muscle cells, we showed previously that the platelet-derived growth factor (PDGF) receptor uses the G-protein, G(i), to stimulate Grb-2-associated phosphoinositide 3-kinase (PI3K) activity. We also showed that this was an intermediate step in the activation of p42/p44 mitogen-activated protein kinase (p42/p44 MAPK) by PDGF. We now present two lines of evidence that provide further support for this model. First, we report that PDGF stimulates the G(i)-mediated tyrosine phosphorylation of the Grb-2 adaptor protein, Gab1. This phosphorylation appears to be necessary for association of PI3K1a with the Gab1-Grb-2 complex. Second, PI3K appears to promote the subsequent association of dynamin II (which is involved in clathrin-mediated endocytic processing) with the complex. Furthermore, inhibitors of PI3K and clathrin-mediated endocytosis reduced the PDGF-dependent activation of p42/p44 MAPK, suggesting a role for PI3K in the endocytic signaling process leading to stimulation of p42/p44 MAPK. Together, these results begin to define a common signaling model for certain growth factor receptors (e.g., PDGF, insulin, insulin-like growth factor-1, and fibroblast growth factor) which use G(i) to transmit signals to p42/p44 MAPK. |
| Databáze: | OpenAIRE |
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