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Gastrin induces tyrosine phosphorylation of Shc proteins and their association with the Grb2/Sos complex
Author(s) -
Seva Catherine,
Kowalski-Chauvel Aline,
Blanchet Jean-Sébastien,
Vaysse Nicole,
Pradayrol Lucien
Publication year - 1996
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(95)01414-4
Subject(s) - grb2 , tyrosine phosphorylation , microbiology and biotechnology , signal transducing adaptor protein , signal transduction , phosphorylation , receptor tyrosine kinase , chemistry , tyrosine , gastrin , sh2 domain , tyrosine kinase , biochemistry , mapk7 , proto oncogene tyrosine protein kinase src , biology , protein kinase c , map kinase kinase kinase , secretion
Gastrin/CCK B G protein‐coupled receptors have been shown to mediate proliferative effects of their endogenous ligands. In the present study, we examined the signal transduction mechanisms linked to the G/CCK B receptor occupancy. We report here that gastrin stimulates MAP kinase activation in a dose‐ and time‐dependent manner, a pathway known to play a key role in cell proliferation. We also characterized the molecular events, upstream of p21‐Ras, that may link the MAP kinase pathway to G/CCK B receptors. Gastrin induced a rapid and transient increase in tyrosine phosphorylation of several proteins including the 2 isoforms (46 and 52 kDa) of the adaptor protein She. Phosphorylated Shc subsequently associated with a complex that includes Grb2 and the p21‐Ras activator, Sos. Our results also indicate that Sos becomes phosphorylated in response to gastrin as shown by a reduction in electrophoretic mobility of the protein. Tyrosine phosphorylation of Shc and subsequent complex formation with Grb2 and Sos appear to be a common mechanism by which tyrosine kinase receptors and the G/CCK B G protein‐coupled receptor stimulate the Ras‐dependent MAP kinase pathway.