1. Src-mediated activation of alpha-diacylglycerol kinase is required for hepatocyte growth factor-induced cell motility
- Author
-
Cutrupi, Santina, Baldanzi, G, Gramaglia, D, Maffè, A, Schaap, D, Giraudo, Enrico, Van, Blitterswijk, W, Bussolino, Federico, Comoglio, Paolo, Graziani, Andrea, Cutrupi, S., Baldanzi, G., Gramaglia, D., Maffe, A., Shaap, D, Giraudo, E., VAN BLITTERSWIJK, W., Bussolino, F., Comoglio, P., and Graziani, Andrea
- Subjects
Diacylglycerol Kinase ,cell migration ,Biology ,Catalysis ,General Biochemistry, Genetics and Molecular Biology ,Receptor tyrosine kinase ,Cell Line ,Cell Movement ,medicine ,Animals ,Humans ,Phosphorylation ,Src tyrosine kinase ,Molecular Biology ,Diacylglycerol Kinase Alpha ,DNA Primers ,Diacylglycerol kinase ,Base Sequence ,General Immunology and Microbiology ,Hepatocyte Growth Factor ,General Neuroscience ,Met ,lipid signaling ,Articles ,Molecular biology ,Cell biology ,Enzyme Activation ,biology.protein ,Tyrosine ,Hepatocyte growth factor ,Signal transduction ,Tyrosine kinase ,Platelet-derived growth factor receptor ,Signal Transduction ,Proto-oncogene tyrosine-protein kinase Src ,medicine.drug - Abstract
Diacylglycerol kinases are involved in cell signaling, either as regulators of diacylglycerol levels or as intracellular signal-generating enzymes. However, neither their role in signal transduction nor their biochemical regulation has been elucidated. Hepatocyte growth factor (HGF), upon binding to its tyrosine kinase receptor, activates multiple signaling pathways stimulating cell motility, scattering, proliferation and branching morphogenesis. Herein we demonstrate that: (i) the enzymatic activity of alpha-diacylglycerol kinase (alphaDgk) is stimulated by HGF in epithelial, endothelial and alphaDgk-transfected COS cells; (ii) cellular expression of an alphaDgk kinase-defective mutant inhibits activation of endogenous alphaDgk acting as dominant negative; (iii) specific inhibition of alphaDgk prevents HGF-induced cell movement of endothelial cells; (iv) HGF induces the association of alphaDgk in a complex with Src, whose tyrosine kinase activity is required for alphaDgk activation by HGF; (v) Src wild type stimulates alphaDgk activity in vitro; and (vi) alphaDgk can be tyrosine phosphorylated in intact cells.
- Published
- 2000