Gastrin-induced DNA synthesis requires p38-MAPK activation via PKC/Ca 2+ and Src-dependent mechanisms

• Published in: FEBS letters Vol. 496; no. 1; pp. 25 - 30
• Main Authors: Dehez, Stephanie, Daulhac, Laurence, Kowalski-Chauvel, Aline, Fourmy, Daniel, Pradayrol, Lucien, Seva, Catherine
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 04-05-2001
• Subjects: Calcium; Cellular proliferation; Gastrin; Mitogen-activated protein kinase; Protein kinase C; Tyrosine kinase; Mitogen-activated protein kinase; Tyrosine kinase; Protein kinase C; Calcium; Cellular proliferation; Gastrin
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/S0014-5793(01)02396-1

We 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 [
3H]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.