Cholecystokinin stimulates the recruitment of the Src-RhoA-phosphoinositide 3-kinase pathway by Vav-2 downstream of G(alpha13) in pancreatic acini.
In isolated rat pancreatic acini, Src, RhoA, PI3-K, Vav-2, G(alpha12), and G(alpha13) were detected by immunoblotting. CCK enhanced the levels of these proteins, and the levels of Src and RhoA were reduced by the Src inhibitor herbimycin A and the Rho inhibitor pravastatin. The PI3-K inhibitor wortmannin reduced the level of PI3-K. These inhibitors also decreased amylase secretion in CCK-treated pancreatic acini without altering basal secretion. Immunoprecipitation studies indicated that CCK caused Src to associate with Vav-2, RhoA, and PI3-K and RhoA and Src to associate with Vav-2. Ras, RasGAP, and SOS did not coimmunoprecipitate with Vav-2, and RasGAP and SOS did not coimmunoprecipitate with RhoA. CCK also enhanced Vav-2 and RhoA to coimmunoprecipitate with G(alpha13). We conclude that CCK stimulates the recruitment of the Src-RhoA-PI3-K signaling pathway by Vav-2 downstream of G(alpha13) in pancreatic acini.
Kim
Minil
M
Second Department of Internal Medicine, Showa University School of Medicine, 1-5-8 Hatanodai Shinagawa-ku, Tokyo 142-8666, Japan.
Nozu
Fumihiko
F
Kusama
Kazushige
K
Imawari
Michio
M
D000681:Amylases / Q000037:antagonists & inhibitors / Q000378:metabolism; D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D016227:Benzoquinones; D002766:Cholecystokinin / Q000494:pharmacology / Q000502:physiology*; D044365:GTP-Binding Protein alpha Subunits, G12-G13 / Q000378:metabolism; D066298:In Vitro Techniques; D047029:Lactams, Macrocyclic; D008297:Male; D046790:Pancreas, Exocrine / Q000187:drug effects / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D017035:Pravastatin / Q000494:pharmacology; D051567:Proto-Oncogene Proteins c-vav / Q000378:metabolism*; D011809:Quinones / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017828:Rifabutin / Q000031:analogs & derivatives; D015398:Signal Transduction; D000077191:Wortmannin; D020742:rhoA GTP-Binding Protein / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019061:src-Family Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
D000681:Amylases; D000730:Androstadienes; D016227:Benzoquinones; D002766:Cholecystokinin; D044365:GTP-Binding Protein alpha Subunits, G12-G13; D047029:Lactams, Macrocyclic; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D017035:Pravastatin; D051567:Proto-Oncogene Proteins c-vav; D011809:Quinones; D017828:Rifabutin; D000077191:Wortmannin; D020742:rhoA GTP-Binding Protein; D019061:src-Family Kinases; C490564:Vav2 protein, rat; C020754:herbimycin