5
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      Src phosphorylates Grb2-associated binder 1 upon hepatocyte growth factor stimulation.

      The Journal of Biological Chemistry

      Adaptor Proteins, Signal Transducing, Animals, Binding Sites, Cell Line, Dogs, Drug Synergism, Embryo, Mammalian, Enzyme Activation, drug effects, Enzyme Inhibitors, pharmacology, Hepatocyte Growth Factor, Humans, Kidney, Mice, Mitogen-Activated Protein Kinases, metabolism, Mutation, NIH 3T3 Cells, Phosphoproteins, Phosphorylation, Protein-Serine-Threonine Kinases, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-akt, Signal Transduction, Transfection, Tyrosine, src Homology Domains, src-Family Kinases, deficiency, genetics

      Read this article at

      ScienceOpenPublisherPubMed
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Grb2-associated binder 1 (Gab1) is known to play an important role in hepatocyte growth factor (HGF) signaling, which rapidly becomes tyrosine-phosphorylated upon HGF stimulation. In this study, we found that the tyrosine phosphorylation of Gab1 in the cells derived from Src/Yes/Fyn null mouse embryos was approximately 40% lower than that in their wild type counterparts upon HGF stimulation. Increased expression of wild-type Src enhanced HGF-induced phosphorylation of Gab1, and, in contrast, expression of the Src kinase-deficient mutant or treatment of the specific Src inhibitor PP1 suppressed it. Expression of a constitutively active Src mutant (Y527F) or oncogenic v-Src led to a prominent increase in Gab1 phosphorylation independent of HGF stimulation. Moreover, Src interacted with Gab1 via both its Src homology 2 and 3 domains and was capable of phosphorylating purified Gab1 in vitro. Finally, the increased phosphorylation of Gab1 by Src selectively potentiated HGF-induced activation of ERK and AKT. Taken together, our results establish a new role for Src in HGF-induced Gab1 phosphorylation.

          Related collections

          Author and article information

          Journal
          12941962
          10.1074/jbc.M305745200

          Comments

          Comment on this article