Document Detail

Specificity and mechanism of protein kinase C activation by sn-1,2-diacylglycerols.
MedLine Citation:
PMID:  3456578     Owner:  NLM     Status:  MEDLINE    
The specificity of protein kinase C activation by sn-1,2-diacylglycerols and analogues was investigated by using a Triton X-100 mixed micellar assay [Hannun, Y. A., Loomis, C. R. & Bell, R. M. (1985) J. Biol. Chem. 260, 10039-10043]. Analogues containing acyl or alkyl chains eight carbons in length were synthesized because sn-1,2-dioctanoylglycerol is an effective cell-permeant activator of protein kinase C. These analogues were tested as activators and antagonists of rat brain protein kinase C to determine the exact structural features important for activity. The analogues established that activation of protein kinase C by diacylglycerols is highly specific. Several analogues established that both carbonyl moieties of the oxygen esters are required for maximal activity and that the 3-hydroxyl moiety is also required. None of the analogues were antagonists. These data, combined with previous investigations, permitted formulation of a model of protein kinase C activation. A three-point attachment of sn-1,2-diacylglycerol to the surface-bound protein kinase C-phosphatidylserine-Ca2+ complex is envisioned to cause activation. Direct ligation of diacylglycerol to Ca2+ is proposed to be an essential step in the mechanism of activation of protein kinase C.
B R Ganong; C R Loomis; Y A Hannun; R M Bell
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  83     ISSN:  0027-8424     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  1986 Mar 
Date Detail:
Created Date:  1986-04-10     Completed Date:  1986-04-10     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1184-8     Citation Subset:  IM    
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MeSH Terms
Brain / enzymology
Diglycerides / pharmacology*
Enzyme Activation / drug effects
Glycerides / pharmacology*
Models, Molecular
Protein Kinase C / metabolism*
Structure-Activity Relationship
Grant Support
Reg. No./Substance:
0/Diglycerides; 0/Glycerides; 0/Micelles; EC Kinase C

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

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