| Threonine phosphorylations induced by RX-871024 and insulin secretagogues in betaTC6-F7 cells. | |
MedLine Citation:
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PMID: 10567013 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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:
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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:
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Type: Journal Article |
Journal Detail:
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Title: The American journal of physiology Volume: 277 ISSN: 0002-9513 ISO Abbreviation: Am. J. Physiol. Publication Date: 1999 Nov |
Date Detail:
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Created Date: 1999-12-14 Completed Date: 1999-12-14 Revised Date: 2007-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0370511 Medline TA: Am J Physiol Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: E862-9 Citation Subset: IM |
Affiliation:
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Endocrine Research, Lilly Research Laboratories, Indianapolis, Indiana 46285, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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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:
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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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