Article abstract
Nature Cell Biology 5, 309 - 319 (2003)
Published online: 24 March 2003 | doi:10.1038/ncb949
There is an Erratum (May 2003) associated with this Article.
A new link between the c-Abl tyrosine kinase and phosphoinositide signalling through PLC-
1
Rina Plattner1, Brenda J. Irvin1,5, Shuling Guo1,6, Kevin Blackburn2, Andrius Kazlauskas3, Robert T. Abraham1,7, John D. York1,4 & Ann Marie Pendergast1
Abstract
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-
1 (PLC-1) is required for c-Abl activation by PDGFR. Decreasing cellular levels of phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P2) by PLC-1-mediated hydrolysis or dephosphorylation by an inositol polyphosphate 5-phosphatase (Inp54) results in increased Abl kinase activity. c-Abl functions downstream of PLC-1, as expression of kinase-inactive c-Abl blocks PLC-1-induced chemotaxis towards PDGF-BB. PLC-1 and c-Abl form a complex in cells that is enhanced by PDGF stimulation. After activation, c-Abl phosphorylates PLC-1 and negatively modulates its function in vivo. These findings uncover a newly discovered functional interdependence between non-receptor Tyr kinase and lipid signalling pathways.
- Department of Pharmacology and Cancer Biology Duke University Medical Center Durham, NC 27710, USA
- Proteomic Technologies GlaxoSmithKline Research Triangle Park, NC 27709, USA
- Schepens Eye Research Institute Harvard Medical School Boston, MA 02114, USA
- Howard Hughes Medical Institute Duke University Medical Center Durham, NC 27710, USA
- Present Address: Department of Biochemistry Vanderbilt University Nashville, TN 37232, USA
- Present Address: Howard Hughes Medical Institute Dept. of Microbiology, Immunology, & Molecular Genetics University of California at Los Angeles, CA 90095, USA
- Present Address: The Burnham Institute 10901 North Torrey Pines Road La Jolla, CA 92037, USA
Correspondence to: Ann Marie Pendergast1 e-mail: pende014@mc.duke.edu
|
MORE ARTICLES LIKE THIS These links to content published by NPG are automatically generated REFERENCE REVIEWS NEWS AND VIEWS RESEARCH |
