Abstract
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.
MeSH terms
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Amylases / antagonists & inhibitors
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Amylases / metabolism
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Androstadienes / pharmacology
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Animals
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Benzoquinones
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Cholecystokinin / pharmacology
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Cholecystokinin / physiology*
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GTP-Binding Protein alpha Subunits, G12-G13 / metabolism
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In Vitro Techniques
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Lactams, Macrocyclic
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Male
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Pancreas, Exocrine / drug effects
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Pancreas, Exocrine / metabolism*
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Phosphatidylinositol 3-Kinases / metabolism*
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Phosphoinositide-3 Kinase Inhibitors
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Pravastatin / pharmacology
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Proto-Oncogene Proteins c-vav / metabolism*
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Quinones / pharmacology
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Rats
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Rats, Sprague-Dawley
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Rifabutin / analogs & derivatives
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Signal Transduction
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Wortmannin
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rhoA GTP-Binding Protein / antagonists & inhibitors
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rhoA GTP-Binding Protein / metabolism*
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src-Family Kinases / antagonists & inhibitors
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src-Family Kinases / metabolism*
Substances
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Androstadienes
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Benzoquinones
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Lactams, Macrocyclic
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Phosphoinositide-3 Kinase Inhibitors
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Proto-Oncogene Proteins c-vav
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Quinones
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Vav2 protein, rat
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Rifabutin
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herbimycin
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Cholecystokinin
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src-Family Kinases
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Amylases
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GTP-Binding Protein alpha Subunits, G12-G13
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rhoA GTP-Binding Protein
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Pravastatin
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Wortmannin