Tyrosine residues 239 and 240 of Shc are phosphatidylinositol 4,5-bisphosphate-dependent phosphorylation sites by c-Src.
In the previous study (Sato K.-I. et al. (1997) FEBS Lett. 410, 136-140), we showed that the phosphorylation of Shc protein by c-Src is dependent on the binding of phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) to the PTB domain of Shc. In this study, we demonstrate that, in contrast to c-Src, v-Src and ... epidermal growth factor (EGF) receptor can phosphorylate Shc in a PtdIns(4,5)P2-independent manner and at different phosphorylation sites. To determine the phosphorylation sites in Shc, we used mutant Shc proteins in which tyrosine residues (Y) 317 and/or 239 and 240 were replaced by phenylalanine residues (F). We found that Y317F Shc but not Y239/240F or Y239/240/317F Shc was phosphorylated by c-Src. The reaction was PtdIns(4,5)P2-dependent and inhibited by the addition of PTB domain of Shc. On the other hand, v-Src and EGF receptor were able to phosphorylate both Y317F and Y239/240F but not Y239/240/317F Shc in a PtdIns(4,5)P2-independent manner. These results highlight the difference between c-Src and v-Src or EGF receptor and suggest that c-Src can phosphorylate predominantly on Tyr239/240 of Shc only when Shc PTB domain is bound to PtdIns(4,5)P2.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Adaptor Proteins, Vesicular Transport, Amino Acid Substitution, Animals, Brain, Carcinoma, Squamous Cell, Cattle, Cell Line, Transformed, ErbB Receptors, Glutathione Transferase, Humans, Mice, Mutagenesis, Site-Directed, Oncogene Protein pp60(v-src), Phosphatidylinositol 4,5-Diphosphate, Protein Kinases, Proteins, Proto-Oncogene Proteins pp60(c-src), Recombinant Fusion Proteins, Shc Signaling Adaptor Proteins, Src Homology 2 Domain-Containing, Transforming Protein 1, Tumor Cells, Cultured, Tyrosine
Adaptor Proteins, Signal Transducing, Adaptor Proteins, Vesicular Transport, Amino Acid Substitution, Animals, Brain, Carcinoma, Squamous Cell, Cattle, Cell Line, Transformed, ErbB Receptors, Glutathione Transferase, Humans, Mice, Mutagenesis, Site-Directed, Oncogene Protein pp60(v-src), Phosphatidylinositol 4,5-Diphosphate, Protein Kinases, Proteins, Proto-Oncogene Proteins pp60(c-src), Recombinant Fusion Proteins, Shc Signaling Adaptor Proteins, Src Homology 2 Domain-Containing, Transforming Protein 1, Tumor Cells, Cultured, Tyrosine
Biochem. Biophys. Res. Commun.
Date: Nov. 17, 1997
PubMed ID: 9388490
View in: Pubmed Google Scholar
Download Curated Data For This Publication
213527
Switch View:
- Interactions 2