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Gastrin‐induced DNA synthesis requires p38‐MAPK activation via PKC/Ca 2+ and Src‐dependent mechanisms
Author(s) -
Dehez Stephanie,
Daulhac Laurence,
Kowalski-Chauvel Aline,
Fourmy Daniel,
Pradayrol Lucien,
Seva Catherine
Publication year - 2001
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/s0014-5793(01)02396-1
Subject(s) - wortmannin , mapk/erk pathway , proto oncogene tyrosine protein kinase src , chemistry , protein kinase c , mitogen activated protein kinase kinase , microbiology and biotechnology , p38 mitogen activated protein kinases , ask1 , gastrin , kinase , protein kinase a , cyclin dependent kinase 2 , map kinase kinase kinase , biology , biochemistry , phosphatidylinositol , secretion
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 [ 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.