Gastrin induces tyrosine phosphorylation of Shc proteins and their association with the Grb2/Sos complex

FEBS Letters

Seva, Catherine¹  Blanchet, Jean-Sébastien¹  Pradayrol, Lucien¹  Vaysse, Nicole¹  Kowalski-Chauvel, Aline¹ 

[1] INSERM U151, Groupe de Recherche de Biologic et Pathologie Digestive, Institut Louis Bugnard, CHU Rangueil, 31054 Toulouse, France

关键词: Gastrin;    G protein-coupled receptor;    MAP kinase;    Shc;    Grb2;    Sos;   

DOI  :  10.1016/0014-5793(95)01414-4

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown