Phogrin, a 60/64 kDa integral membrane protein localized to dense-core secretory granules of neuroendocrine cells, was found to be reversibly phosphorylated in intact pancreatic β-cells. Phosphorylation occurred in response to a variety of secretory stimuli, including glucose and depolarizing concentrations of K+. In MIN6 cells, the glucose dose-response and time course of phogrin phosphorylation paralleled that of insulin secretion. Like secretion, glucose- or K+-stimulated phosphorylation required the presence of Ca2+. The calmodulin antagonist W-7 and the Ca2+/calmodulin-dependent kinase II inhibitor KN-93 dose-dependently inhibited both phosphorylation and secretion, while the ‘inactive’ analogue KN-92 was effective only at significantly higher concentrations. Phosphorylation of phogrin was also stimulated in cells exposed to forskolin, an effect presumably mediated by protein kinase A (cAMP-dependent protein kinase). Under these conditions, phogrin phosphorylation could be dissociated from the secretory response. In MIN6 cells, as in pancreatic islets, cAMP potentiates rather than initiates insulin release. Thus our observations are consistent with a role for phogrin phosphorylation in the signal-transduction pathway at a site proximal to the exocytic event itself, possibly regulating secretory-granule mobilization and recruitment to the exocytic site.
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Research Article|
July 26 1999
Secretagogue-dependent phosphorylation of phogrin, an insulin granule membrane protein tyrosine phosphatase homologue
Christina WASMEIER;
Christina WASMEIER
1Barbara Davis Center for Childhood Diabetes, University of Colorado Health Sciences Center, 4200 East 9th Ave., Denver 80262, CO, U.S.A.
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John C. HUTTON
John C. HUTTON
1
1Barbara Davis Center for Childhood Diabetes, University of Colorado Health Sciences Center, 4200 East 9th Ave., Denver 80262, CO, U.S.A.
1To whom correspondence should be addressed (e-mail john.hutton@uchsc.edu).
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Publisher: Portland Press Ltd
Received:
March 09 1999
Revision Received:
April 27 1999
Accepted:
May 17 1999
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London © 1999
1999
Biochem J (1999) 341 (3): 563–569.
Article history
Received:
March 09 1999
Revision Received:
April 27 1999
Accepted:
May 17 1999
Citation
Christina WASMEIER, John C. HUTTON; Secretagogue-dependent phosphorylation of phogrin, an insulin granule membrane protein tyrosine phosphatase homologue. Biochem J 1 August 1999; 341 (3): 563–569. doi: https://doi.org/10.1042/bj3410563
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