Journal
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
Volume 1763, Issue 4, Pages 356-365Publisher
ELSEVIER
DOI: 10.1016/j.bbamcr.2006.03.004
Keywords
pancreas; src; src kinase; lyn; cholecystokinin; pancreatic secretion; pancreatic growth; pancreatic growth factor
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Src family kinases (SFK) play a central signaling role for growth factors, cytokines, G-protein-coupled receptors and other stimuli. SFKs play important roles in pancreatic acinar cell secretion, endocytosis, growth, cytoskeletal integrity and apoptosis, although little is known of the specific SFKs involved. In this study we demonstrate the SFK, Lyn, is present in rat pancreatic acini and investigate its activation/signaling. Ca2+-mobilizing agents, cAMP-mobilizing agents and pancreatic growth factors activated Lyn. CCK, a physiological regulator of pancreatic function, rapidly activated Lyn. The specific SFK inhibitor, PP2, decreased Lyn activation; however, the inactive analogue, PP3, bad no effect. Inhibition of CCKstimulated changes in [Ca2+](i) decreased Lyn activation by 55%; GFX, a PKC inhibitor by 36%; and the combination by 95%. CCK activation of Lyn required stimulation of high and low affinity CCKA receptor states. CCK stimulated an association of Lyn with PKC-delta, She, p 125(FAK) and PYK2 as well as with their autophosphorylated forms, but not with Cb1, p85, p 130(CAS) or ERK 1/2. These results show Lyn is activated by diverse pancreatic stimulants. CCK's activation of Lyn is likely an important mediator of its ability to cause tyrosine phosphorylation of numerous important cellular mediators such as p125(FAK), PYK2, PKC-delta and She, which play central roles in CCK's effects on acinar cell function. Published by Elsevier B.V.
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