期刊
BIOCHEMICAL PHARMACOLOGY
卷 67, 期 1, 页码 135-146出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bcp.2003.08.015
关键词
tyrosine phosphorylation; colon cancer; gastrin; CCK2 receptor; G protein-coupled receptor; signal transduction
Although the expression of CCK2 receptors is widely reported in human colorectal cancers, little is known on its role in mediating the proliferative effects of mature amidated gastrin (G17 amide) on colorectal cancers. The purpose of the present study was to determine the effects of G 17 amide on tyrosine phosphorylation of focal adhesion kinase (FAK), paxillin, and p 130 Crk-associated substrate (p130(Cas)) in Colo 320 cells, a human colorectal cancer cell line which expresses CCK2 receptors. By immunoprecipitation and immunoblotting, an increase in tyrosine phosphorylation of FAK (tyrosine-397), paxillin (tyrosine-31), and p130(Cas) was detected in a time- and dose-dependent manner. Overexpression of CCK2 receptors in Colo 320 cells (Colo 320 WT) by stable transfection with the human CCK2 receptor cDNA resulted in an increased tyrosine phosphorylation of FAK, paxillin, and p130(Cas). After incubation with 1 muM L-365,260, a specific CCK2 receptor antagonist, this increase was completely inhibited. Our results demonstrate that in human colon cancer cells, gastrin caused a rapid tyrosine phosphorylation of FAK, paxillin, and p130(Cas) by activation of CCK2 receptor. The phosphorylation of these proteins might be important in mediating gastrin effects on proliferation, apoptosis, and metastasis. (C) 2003 Elsevier Inc. All rights reserved.
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