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PMID: 7821735 Published · ppublish English Biography Historical Article Journal Article Portrait Research Support, Non-U.S. Gov't Review

Protein phosphorylation and beta-cell function.

Diabetologia ·Vol. 37 Suppl 2 ·1994-09-00 ·Pages S21-9

Ashcroft SJ

Abstract

The central role of reversible protein phosphorylation in regulation of beta-cell function is reviewed and the properties of the protein kinases so far defined in beta cells are summarised. The key effect of Ca2+ to initiate insulin secretion involves activation of a Ca2+/calmodulin-dependent protein kinase. Potentiation of secretion by agents activating protein kinase A or C appears to involve an increase in the sensitivity of the secretory system to intracellular Ca2+. The effects of MgATP on the binding of [3H]-glibenclamide to the beta-cell sulphonylurea receptor suggest that the properties of this receptor, which controls the activity of ATP-sensitive K-channels, are modulated by phosphorylation. The identity of the kinases and phosphatases responsible is not known but the presence in beta-cell membranes of various kinases not dependent on Ca2+ or cyclic AMP, and including tyrosine kinase, is documented, together with the presence of both Ca(2+)-dependent and Ca(2+)-independent protein phosphatases. Protein phosphorylation is also involved in regulation of beta-cell Ca2+ fluxes and evidence is presented that protein kinase C activation inhibits Ca2+ signalling by reducing influx of Ca2+ into the beta cell. The identity of the Ca2+/calmodulin-dependent protein kinase activity in beta cells is discussed. Comparison of its properties towards substrates and inhibitors with those of brain Ca2+/calmodulin-dependent protein kinase II suggests that the beta-cell enzyme may be similar or identical to the brain enzyme.(ABSTRACT TRUNCATED AT 250 WORDS)

MeSH Terms
ATP-Binding Cassette Transporters Adenosine Triphosphate/pharmacology Animals Awards and Prizes Brain/enzymology Calcium/metabolism Diabetes Mellitus/history Europe Glyburide/metabolism History, 20th Century Humans Insulin/metabolism Insulin Secretion Islets of Langerhans/physiology Models, Biological Phosphorylation Potassium/pharmacology Potassium Channels/drug effects,metabolism,physiology Potassium Channels, Inwardly Rectifying Protein Kinase C/metabolism Protein Kinases/metabolism Receptors, Drug/drug effects,metabolism Signal Transduction Societies, Medical Sulfonylurea Receptors United Kingdom
Chemicals
ATP-Binding Cassette Transporters Insulin Potassium Channels Potassium Channels, Inwardly Rectifying Receptors, Drug Sulfonylurea Receptors Adenosine Triphosphate Protein Kinases Protein Kinase C Potassium Glyburide Calcium
Authors & Affiliations
1 authors, click to expand affiliations / ORCID
Ashcroft S J
Nuffield Department of Clinical Biochemistry, John Radcliffe Hospital, Oxford, UK.
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Article Info
Journal
Diabetologia
Abbr.
Diabetologia
ISSN
0012-186X
DOI
10.1007/BF00400822
Published
1994-09-00
Pages
S21-9
Language
English
Region
Germany
NLM ID
0006777
Subset
IM
External Links
PubMed source DOI: 10.1007/BF00400822 View journal details
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