Regulation of inositol lipid-specific phospholipase cdelta by changes in Ca2+ ion concentrations.
Studies of inositol lipid-specific phospholipase C (PLC) have elucidated the main regulatory pathways for PLCbeta and PLCgamma but the regulation of PLCdelta isoenzymes still remains obscure. Here we demonstrate that an increase in Ca2+ ion concentration within the physiological range (0.1-10 microM) is sufficient to stimulate PLCdelta1, but not PLCgamma1 and PLCbeta1, to hydrolyse cellular inositol lipids present in permeabilized cells. The activity of PLCdelta1 is further enhanced in the presence of phosphatidylinositol transfer protein (PI-TP). Both full activation by Ca2+ ions and stimulation in the presence of PI-TP require an intact PH domain involved in the membrane attachment of PLCdelta1. The physiological implication of this study is that PLCdelta1 could correspond to a previously uncharacterized PLC responsible for Ca2+ ion-stimulated inositol lipid hydrolysis observed in many cellular systems.
Allen
V
V
CRC Centre for Cell and Molecular Biology, Chester Beatty Laboratories, Fulham Road, London SW3 6JB, U.K.
Swigart
P
P
Cheung
R
R
Cockcroft
S
S
Katan
M
M
D000818:Animals; D001921:Brain / Q000201:enzymology*; D019556:COS Cells; D002118:Calcium / Q000494:pharmacology*; D002352:Carrier Proteins / Q000378:metabolism; D002417:Cattle; D002463:Cell Membrane Permeability; D003001:Cloning, Molecular; D015971:Gene Expression Regulation, Enzymologic; D018922:HL-60 Cells; D006801:Humans; D007527:Isoenzymes / Q000096:biosynthesis / Q000378:metabolism*; D007700:Kinetics; D008565:Membrane Proteins; D016716:PC12 Cells; D010716:Phosphatidylinositols / Q000378:metabolism*; D051966:Phospholipase C gamma; D049294:Phospholipid Transfer Proteins; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D013379:Substrate Specificity; D014162:Transfection; D010738:Type C Phospholipases / Q000096:biosynthesis / Q000378:metabolism*
D002352:Carrier Proteins; D007527:Isoenzymes; D008565:Membrane Proteins; D010716:Phosphatidylinositols; D049294:Phospholipid Transfer Proteins; D011994:Recombinant Proteins; C118289:SEC24 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D010738:Type C Phospholipases; D051966:Phospholipase C gamma; D002118:Calcium