Document Detail


Threonine phosphorylations induced by RX-871024 and insulin secretagogues in betaTC6-F7 cells.
MedLine Citation:
PMID:  10567013     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Treatment of the pancreatic beta-cell line betaTC6-F7 with an imidazoline compound, RX-871024, KCl, or tolbutamide resulted in increased threonine phosphorylation of a 220-kDa protein (p220) concurrent with enhanced insulin secretion, which can be partially antagonized by diazoxide, an ATP-sensitive potassium (K(ATP)) channel activator. Although phosphorylation of p220 was regulated by cytoplasmic free calcium concentration ([Ca(2+)](i)), membrane depolarization alone was not sufficient to induce phosphorylation. Phosphorylation of p220 also was not directly mediated by protein kinase A, protein kinase C, or insulin exocytosis. Analysis of subcellular fractions indicated that p220 is a hydrophilic protein localized exclusively in the cytosol. Subsequently, p220 was purified to homogeneity, sequenced, and identified as nonmuscle myosin heavy chain-A (MHC-A). Stimulation of threonine phosphorylation of nonmuscle MHC-A by KCl treatment also resulted in increased phosphorylation of a 40-kDa protein, which was coimmunoprecipitated by antibody to MHC-A. Our results suggest that both nonmuscle MHC-A and the 40-kDa protein may play roles in regulating signal transduction, leading to insulin secretion.
Authors:
J An; G Zhao; L M Churgay; J J Osborne; J E Hale; G W Becker; G Gold; L E Stramm; Y Shi
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  The American journal of physiology     Volume:  277     ISSN:  0002-9513     ISO Abbreviation:  Am. J. Physiol.     Publication Date:  1999 Nov 
Date Detail:
Created Date:  1999-12-14     Completed Date:  1999-12-14     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0370511     Medline TA:  Am J Physiol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  E862-9     Citation Subset:  IM    
Affiliation:
Endocrine Research, Lilly Research Laboratories, Indianapolis, Indiana 46285, USA.
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Animals
Antihypertensive Agents / pharmacology
Calcium / metabolism
Calcium Channel Blockers / pharmacology
Calcium Channels / physiology
Cell Line
Cyclic AMP-Dependent Protein Kinases / metabolism
Cytosol / chemistry,  enzymology
Diazoxide / pharmacology
Exocytosis / physiology
Humans
Hypoglycemic Agents / pharmacology*
Imidazoles / pharmacology*
Indoles / pharmacology*
Insulin / secretion*
Islets of Langerhans / cytology,  drug effects*,  enzymology
Isomerism
Membrane Potentials / drug effects
Membrane Proteins / analysis,  metabolism
Myosin Heavy Chains / analysis,  chemistry
Nifedipine / pharmacology
Phosphorylation
Potassium Chloride / pharmacology
Protein Kinase C / metabolism
Subcellular Fractions / chemistry
Threonine / metabolism*
Tolbutamide / pharmacology*
Chemical
Reg. No./Substance:
0/2-(2-imidazolin-2-yl)-1-phenyl-1H-indole; 0/Antihypertensive Agents; 0/Calcium Channel Blockers; 0/Calcium Channels; 0/Hypoglycemic Agents; 0/Imidazoles; 0/Indoles; 0/Membrane Proteins; 0/Myosin Heavy Chains; 11061-68-0/Insulin; 21829-25-4/Nifedipine; 364-98-7/Diazoxide; 64-77-7/Tolbutamide; 72-19-5/Threonine; 7440-70-2/Calcium; 7447-40-7/Potassium Chloride; EC 2.7.11.11/Cyclic AMP-Dependent Protein Kinases; EC 2.7.11.13/Protein Kinase C

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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