A new link between the c-Abl tyrosine kinase and phosphoinositide signalling through PLC-gamma1.
Published
Journal Article
The c-Abl tyrosine (Tyr) kinase is activated after platelet-derived-growth factor receptor (PDGFR) stimulation in a manner that is partially dependent on Src kinase activity. However, the activity of Src kinases alone is not sufficient for activation of c-Abl by PDGFR. Here we show that functional phospholipase C-gamma1 (PLC-gamma1) is required for c-Abl activation by PDGFR. Decreasing cellular levels of phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P2) by PLC-gamma1-mediated hydrolysis or dephosphorylation by an inositol polyphosphate 5-phosphatase (Inp54) results in increased Abl kinase activity. c-Abl functions downstream of PLC-gamma1, as expression of kinase-inactive c-Abl blocks PLC-gamma1-induced chemotaxis towards PDGF-BB. PLC-gamma1 and c-Abl form a complex in cells that is enhanced by PDGF stimulation. After activation, c-Abl phosphorylates PLC-gamma1 and negatively modulates its function in vivo. These findings uncover a newly discovered functional interdependence between non-receptor Tyr kinase and lipid signalling pathways.
Full Text
Duke Authors
Cited Authors
- Plattner, R; Irvin, BJ; Guo, S; Blackburn, K; Kazlauskas, A; Abraham, RT; York, JD; Pendergast, AM
Published Date
- April 2003
Published In
Volume / Issue
- 5 / 4
Start / End Page
- 309 - 319
PubMed ID
- 12652307
Pubmed Central ID
- 12652307
International Standard Serial Number (ISSN)
- 1465-7392
Digital Object Identifier (DOI)
- 10.1038/ncb949
Language
- eng
Conference Location
- England