A-Raf associates with and regulates platelet-derived growth factor receptor signalling
| Autor: | Andrea D. Hawrysh, Ryaz Chagpar, Elizabeth S. Mahon, Lindsey M. Johnson, Deborah H. Anderson |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
MAPK/ERK pathway
Proto-Oncogene Proteins A-raf Receptor tyrosine kinase Mice Phosphatidylinositol 3-Kinases Growth factor receptor Chlorocebus aethiops Animals Humans Receptors Platelet-Derived Growth Factor Phosphorylation biology Phospholipase C gamma Chemistry Autophosphorylation JAK-STAT signaling pathway Cell Biology Cell biology ErbB Receptors Proto-Oncogene Proteins c-raf Organ Specificity Type C Phospholipases COS Cells Mutation NIH 3T3 Cells biology.protein Cancer research Tyrosine kinase Platelet-derived growth factor receptor Signal Transduction Proto-oncogene tyrosine-protein kinase Src |
| Zdroj: | Cellular Signalling. 17:857-868 |
| ISSN: | 0898-6568 |
| DOI: | 10.1016/j.cellsig.2004.11.006 |
| Popis: | Raf kinases are important intermediates in epidermal growth factor (EGF) and platelet-derived growth factor (PDGF) mediated activation of the mitogen-activated protein kinase (MAPK) pathway. In this report, we show that the A-Raf kinase is associated with activated EGF receptor complexes and with PDGF receptor (PDGFR) complexes independent of prior PDGF treatment. The ability of A-Raf to associate with receptor tyrosine kinases could provide a Ras-GTP-independent mechanism for the membrane localization of A-Raf. Expression of a partially activated A-Raf mutant resulted in decreased tyrosine phosphorylation of the PDGFR, specifically on Y857 (autophosphorylation site) and Y1021 (phospholipase Cgamma1 (PLCgamma1) binding site), but not the binding sites for other signalling proteins (Nck, phosphatidylinositol 3'-kinase (PI3K), RasGAP, Grb2, SHP). Activated A-Raf expression also altered the activation of PLCgamma1, and p85-associated PI3K. Thus, A-Raf can regulate PLCgamma1 signalling via a PDGFR-dependent mechanism and may also regulate PI3K signalling via a PDGFR-independent mechanism. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect