Cck activates p90rsk in rat pancreatic acini through protein kinase
c.
Bragado, M. Julia, Andrzej Dabrowski, Guy E. Groblewski, and John A.
Williams.
Departments of Physiology and Internal Medicine, University of
Michigan, Ann Arbor, Michigan 48109-0622
APStracts 3:0162G, 1996.
Western blotting and immunoprecipitation with anti p90rsk revealed the
presence of this S6 kinase (p90rsk) in isolated rat pancreatic acini.
CCK activated p90rsk activity in a time and dose-dependent manner and
increased its phosphorylation. The threshold concentration of CCK was
10 pM and the maximal effect was seen at 1?nM. An increase in p90rsk
was observed 1 min after 1 nM CCK stimulation, reaching a maximum at
10 min, when p90rsk activity was increased by 5.4 fold. Carbachol and
bombesin, but not vasoactive intestinal peptide (VIP) also activated
p90rsk. CCK-induced activation of p90rsk appears mediated by protein
kinase C (PKC), since 12-O-tetradecanoylphorbol 13-acetate (TPA)
increased p90rsk activity by 5.3 fold. GF-109293X, a potent inhibitor
of PKC strongly inhibited CCK-evoked p90rsk activity. Treatment of
acini with ionomycin or BAPTA had no effect, indicating that
mobilization of intracellular calcium by CCK is not important in
p90rsk activation. While there were some quantitative differences in
the extent of inhibition, there was a general parallelism in the
effect of the specific inhibitors (rapamycin, wortmannin, MEK
inhibitor PD98059 and GF-109293X) on p90rsk and p42mapk activities,
consistent with a model where p90rsk can be regulated in acini by MAP
kinases.
Received 25 April 1996; accepted in final form 5 August 1996.
APS Manuscript Number G160-6.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 29 August 1996