Isozyme-selective stimulation of phospholipase C-beta 2 by G protein beta gamma-subunits.
Hydrolysis by phospholipase C (PLC) of phosphatidylinositol 4,5-bisphosphate is a key mechanism by which many extracellular signalling molecules regulate functions of their target cells. At least eight distinct isozymes of PLC are recognized in mammalian cells. Receptor-controlled PLC is often regulated by G proteins, which can be modified by pertussis toxin in some cells but not in others. In the latter cells, PLC-beta 1, but not PLC-gamma 1 or PLC-delta 1, may be activated by members of the alpha q-subfamily of the G protein alpha-subunits. An unidentified PLC in soluble fractions of cultured human HL-60 granulocytes is specifically stimulated by G protein beta gamma subunits purified from retina and brain. Identification of a second PLC-beta complementary DNA (PLC-beta 2) in an HL-60 cell cDNA library prompted us to investigate the effect of purified G protein beta gamma subunits on the activities of PLC-beta 1 and PLC-beta 2 transiently expressed in cultured mammalian cells. We report here that PLC-beta 1 and PLC-beta 2 were stimulated by free beta gamma subunits and that PLC-beta 2 was the most sensitive to beta gamma stimulation. Thus stimulation of PLC by beta gamma subunits is isozyme-selective and PLC-beta 2 is a prime target of beta gamma stimulation. Activation of PLC-beta 2 by beta gamma subunits may be an important mechanism by which pertussis toxin-sensitive G proteins stimulate PLC.
Camps
M
M
Molecular Pharmacology Division, German Cancer Research Center, Heidelberg.
Carozzi
A
A
Schnabel
P
P
Scheer
A
A
Parker
P J
PJ
Gierschik
P
P
D000818:Animals; D002460:Cell Line; D019204:GTP-Binding Proteins / Q000378:metabolism*; D005822:Genetic Vectors; D007295:Inositol Phosphates / Q000378:metabolism; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D007700:Kinetics; D046911:Macromolecular Substances; D010957:Plasmids; D011994:Recombinant Proteins / Q000378:metabolism; D014162:Transfection; D010738:Type C Phospholipases / Q000235:genetics / Q000378:metabolism*
D007295:Inositol Phosphates; D007527:Isoenzymes; D046911:Macromolecular Substances; D011994:Recombinant Proteins; D010738:Type C Phospholipases; D019204:GTP-Binding Proteins