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Rapid tyrosine phosphorylation of focal adhesion kinase, paxillin, and p130Cas by gastrin in human colon cancer cells
- Source :
- Biochemical Pharmacology. 67:135-146
- Publication Year :
- 2004
- Publisher :
- Elsevier BV, 2004.
-
Abstract
- Although the expression of CCK(2) 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 G17 amide on tyrosine phosphorylation of focal adhesion kinase (FAK), paxillin, and p130 Crk-associated substrate (p130(Cas)) in Colo 320 cells, a human colorectal cancer cell line which expresses CCK(2) 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 CCK(2) receptors in Colo 320 cells (Colo 320 WT) by stable transfection with the human CCK(2) receptor cDNA resulted in an increased tyrosine phosphorylation of FAK, paxillin, and p130(Cas). After incubation with 1 microM L-365,260, a specific CCK(2) 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 CCK(2) receptor. The phosphorylation of these proteins might be important in mediating gastrin effects on proliferation, apoptosis, and metastasis.
- Subjects :
- PTK2
macromolecular substances
Biochemistry
Focal adhesion
chemistry.chemical_compound
Gastrins
Tumor Cells, Cultured
Humans
Phosphorylation
Tyrosine
Paxillin
Gastrin
Pharmacology
Retinoblastoma-Like Protein p130
biology
digestive, oral, and skin physiology
Proteins
Tyrosine phosphorylation
Protein-Tyrosine Kinases
Phosphoproteins
Receptor, Cholecystokinin B
Cytoskeletal Proteins
Crk-Associated Substrate Protein
chemistry
Focal Adhesion Kinase 1
Focal Adhesion Protein-Tyrosine Kinases
Colonic Neoplasms
embryonic structures
biology.protein
Cancer research
biological phenomena, cell phenomena, and immunity
Signal transduction
hormones, hormone substitutes, and hormone antagonists
Densitometry
Subjects
Details
- ISSN :
- 00062952
- Volume :
- 67
- Database :
- OpenAIRE
- Journal :
- Biochemical Pharmacology
- Accession number :
- edsair.doi.dedup.....98f9f8bf1d714791dfadf6f444966d10