Document Detail

D-myo-inositol 1,4,5-trisphosphate inhibits binding of phospholipase C-delta 1 to bilayer membranes.
MedLine Citation:
PMID:  8294445     Owner:  NLM     Status:  MEDLINE    
The binding of phosphoinositide-specific phospholipase C-delta 1 (PLC-delta 1) to bilayer membranes composed of phosphatidylcholine (PC) and phosphatidylinositol 4,5-bisphosphate (PIP2) was measured in the presence or absence of inositol phosphates. Binding was inhibited by the natural D-isomer of myo-inositol 1,4,5-trisphosphate (D-InsP3), but not by the L-isomer. The concentration of D-InsP3 required to decrease binding by 50% was 5.4 +/- 0.5 microM. 1-(alpha-Glycerophosphoryl)-D-myo-inositol 4,5-bisphosphate and D-myo-inositol 2,4,5-trisphosphate were nearly as effective as D-Ins(1,4,5)P3. D-myo-inositol monophosphate with phosphate esterified at either positions 1 or 2 of the myo-inositol ring, had no significant effect on binding. D-myo-inositol 1,4-bisphosphate weakly inhibited the binding, whereas the 4,5-isomer was nearly as potent as D-InsP3. Neither ATP nor inorganic phosphate significantly affected binding. As expected, D-Ins(1,4,5)P3 but not L-Ins(1,4,5)P3 decreased the initial rate of PIP2 hydrolysis in bilayer vesicles. The concentration required to decrease hydrolysis by 50% was 12.4 +/- 0.5 microM. A catalytic fragment of PLC-delta 1 that lacks a domain necessary for high affinity PIP2 binding was prepared as previously described (Cifuentes, M. E., Honkanen, L., and Rebecchi, M. J. (1993) J. Biol. Chem. 268, 11586-11593). In contrast to the native enzyme, the rate of PIP2 hydrolysis, catalyzed by the fragment, was not affected by D-Ins(1,4,5)P3. These data suggest that high affinity binding of the enzyme to PIP2 and processive catalysis, involve specific recognition of the 4- and 5-position phosphates of the inositol ring. Our results are consistent with feedback inhibition by the polar head group product, D-Ins(1,4,5)P3, at a step that precedes catalysis, namely interfacial recognition.
M E Cifuentes; T Delaney; M J Rebecchi
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  269     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  1994 Jan 
Date Detail:
Created Date:  1994-02-25     Completed Date:  1994-02-25     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1945-8     Citation Subset:  IM    
Department of Physiology and Biophysics, State University of New York, Stony Brook 11794.
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MeSH Terms
Brain / enzymology
Cytosol / enzymology
Inositol 1,4,5-Trisphosphate / pharmacology*
Inositol Phosphates / pharmacology
Isoenzymes / antagonists & inhibitors,  metabolism*
Lipid Bilayers / metabolism*
Phosphatidylinositol 4,5-Diphosphate
Phosphatidylinositol Diacylglycerol-Lyase
Phosphatidylinositol Phosphates / metabolism
Phosphoric Diester Hydrolases / metabolism*
Type C Phospholipases / antagonists & inhibitors,  metabolism*
Grant Support
Reg. No./Substance:
0/Inositol Phosphates; 0/Isoenzymes; 0/Lipid Bilayers; 0/Phosphatidylinositol 4,5-Diphosphate; 0/Phosphatidylinositol Phosphates; 85166-31-0/Inositol 1,4,5-Trisphosphate; EC 3.1.4.-/Phosphoric Diester Hydrolases; EC 3.1.4.-/Type C Phospholipases; EC Diacylglycerol-Lyase

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

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