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Shp-2 tyrosine phosphatase is required for hepatocyte growth factor-induced activation of sphingosine kinase and migration in embryonic fibroblasts
- Source :
-
Cellular Signalling . Nov2006, Vol. 18 Issue 11, p2049-2055. 7p. - Publication Year :
- 2006
-
Abstract
- Abstract: Shp-2, a ubiquitously expressed protein tyrosine phosphatase containing two Src homology 2 domains, plays an important role in integrating signaling from the cell surface receptors to intracellular signaling mechanisms. Previous studies have demonstrated that the Shp-2 is involved in hepatocyte growth factor (HGF)-induced cell scattering. Here we report that Shp-2 is required for the HGF-induced activation of sphingosine kinase-1 (SPK1), a highly conserved lipid kinase that plays an important role in cell migration. Loss-of-function mutation of Shp-2 did not affect the expression of SPK1, but resulted in its inactivation and the blockage of HGF-induced migration in embryonic fibroblasts. Reintroduction of functional wild type (WT) Shp-2 into the mutant cells partially restored SPK1 activation, and overexpression of SPK1 in these mutant cells enhanced HGF-induced cell migration. Inhibition of expression or activity of SPK1 in WT cells markedly decreased intracellular S1P levels and HGF-induced cell migration. Furthermore, we found that Shp-2 co-immunoprecipitated with SPK1 and c-Met in embryonic fibroblasts. These studies suggest that Shp-2 is an SPK1-interacting protein and that it plays an indispensable role in HGF-induced SPK1 activation. [Copyright &y& Elsevier]
- Subjects :
- *TYROSINE
*CYTOKINES
*GROWTH factors
*FIBROBLASTS
Subjects
Details
- Language :
- English
- ISSN :
- 08986568
- Volume :
- 18
- Issue :
- 11
- Database :
- Academic Search Index
- Journal :
- Cellular Signalling
- Publication Type :
- Academic Journal
- Accession number :
- 22636233
- Full Text :
- https://doi.org/10.1016/j.cellsig.2006.04.002