Src kinase pathways in extracellular Ca(2+)-dependent pancreatic enzyme secretion.
We investigated the functional roles of Src kinase pathways in rat pancreatic acinar cells. CCK-8 dose-dependently increased Src kinase activities by a mechanism that was sensitive to herbimycin A. CCK-8 enhanced protein tyrosine kinase (PTK) activities when the synthetic Src peptide was used as a substrate. Increased PTK activities, sustained Ca2+ entry, and amylase secretion, all stimulated by CCK-8, were abolished by eliminating extracellular Ca2+ ([Ca2+]o). CCK-8 caused tyrosine phosphorylation of three major proteins: 60 KDa, 85 KDa, and 105 KDa. The elimination of [Ca2+]o prevented the tyrosine phosphorylations of p60 and p105, but not p85. Therefore, the p60 Src kinase and the p105 kinase, referred to as "Src kinase kinase', may be involved in [Ca2+]o-dependent pancreatic exocytosis.
Tsunoda
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Y
Department of Internal Medicine, University of Michigan, Ann Arbor 48109-0682, USA.
Yoshida
H
H
Africa
L
L
Steil
G J
GJ
Owyang
C
C
D000681:Amylases / Q000037:antagonists & inhibitors / Q000378:metabolism; D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D016227:Benzoquinones; D002118:Calcium / Q000378:metabolism*; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019833:Genistein; D007529:Isoflavones / Q000494:pharmacology; D047029:Lactams, Macrocyclic; D008297:Male; D010179:Pancreas / Q000166:cytology / Q000201:enzymology*; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives / Q000378:metabolism; D010766:Phosphorylation; D011809:Quinones / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017828:Rifabutin / Q000031:analogs & derivatives; D012844:Sincalide / Q000494:pharmacology; D013379:Substrate Specificity; D000077191:Wortmannin; D019061:src-Family Kinases / Q000378:metabolism*
D000730:Androstadienes; D016227:Benzoquinones; D004791:Enzyme Inhibitors; D007529:Isoflavones; D047029:Lactams, Macrocyclic; D011809:Quinones; C011867:4-hydroxyphenylethanol; D017828:Rifabutin; C020754:herbimycin; D019833:Genistein; D019061:src-Family Kinases; D000681:Amylases; D012844:Sincalide; D010626:Phenylethyl Alcohol; D002118:Calcium; D000077191:Wortmannin