Gastrin‐induced DNA synthesis requires p38‐MAPK activation via PKC/Ca 2+ and Src‐dependent mechanisms
2001; Wiley; Volume: 496; Issue: 1 Linguagem: Inglês
10.1016/s0014-5793(01)02396-1
ISSN1873-3468
AutoresStéphanie Dehez, Laurence Daulhac, Aline Kowalski‐Chauvel, Daniel Fourmy, Lucien Pradayrol, Catherine Seva,
Tópico(s)Ion Transport and Channel Regulation
ResumoWe present evidence that gastrin, binding to a G protein‐coupled receptor, activates the p38‐mitogen‐activated protein kinase (MAPK) pathway. Blockage of protein kinase C (PKC) by GF109203X, depletion of intracellular calcium by thapsigargin or inhibition of Src family kinases by PP2 prevented p38‐MAPK activation and the Src kinase activity stimulated by gastrin. Inhibition of the PI 3‐kinase by wortmannin or LY294002 did not affect these responses. In addition, the p38‐MAPK inhibitor, SB203580, repressed gastrin‐induced [ 3 H]thymidine incorporation, indicating a major role of p38‐MAPK in the growth‐promoting effect of gastrin. Our results demonstrate that gastrin‐induced DNA synthesis requires p38‐MAPK activation through mechanisms that involve calcium mobilization, PKC and Src family kinases.
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