Activation of the beta 1 isozyme of phospholipase C by alpha subunits of the Gq class of G proteins.
Many hormones, neurotransmitters and growth factors, on binding to G protein-coupled receptors or receptors possessing tyrosine kinase activity, increase intracellular levels of the second messengers inositol 1,4,5-trisphosphate and 1,2-diacylglycerol. This is due to activation of phosphoinositide-specific phospholipase(s) C (PLC), the isozymes of which are classified into groups, alpha, beta, gamma and delta. The beta, gamma and delta groups themselves contain PLC isozymes which have both common and unique structural domains. Only the gamma 1 isozyme has been implicated in a signal transduction mechanism. This involves association with, and tyrosine phosphorylation by, the ligand-bound epidermal growth factor and platelet-derived growth factor receptors, probably by means of the PLC-gamma 1-specific src homology (SH2) domain. Because EGF receptor-mediated tyrosine phosphorylation of PLC-gamma 1 stimulates catalytic activity in vitro and G proteins have been implicated in the activation of PLC, we investigated which PLC isozymes are subject to G protein regulation. We have purified an activated G protein alpha subunit that stimulates partially purified phospholipase C and now report that this G protein specifically activates the beta 1 isozyme, but not the gamma 1 and delta 1 isozymes of phospholipase C. We also show that this protein is related to the Gq class of G protein alpha subunits.
Taylor
S J
SJ
Howard Hughes Medical Institute, Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232.
Chae
H Z
HZ
Rhee
S G
SG
Exton
J H
JH
D000818:Animals; D001665:Binding Sites; D002118:Calcium / Q000494:pharmacology; D002417:Cattle; D002462:Cell Membrane / Q000737:chemistry; D004789:Enzyme Activation / Q000187:drug effects; D066246:ErbB Receptors / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000494:pharmacology* / Q000502:physiology; D007527:Isoenzymes / Q000378:metabolism*; D008099:Liver / Q000737:chemistry; D046911:Macromolecular Substances; D008970:Molecular Weight; D019000:Phosphotyrosine; D011956:Receptors, Cell Surface / Q000378:metabolism; D017479:Receptors, Platelet-Derived Growth Factor; D015290:Second Messenger Systems; D015398:Signal Transduction; D010738:Type C Phospholipases / Q000378:metabolism*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D007527:Isoenzymes; D046911:Macromolecular Substances; D011956:Receptors, Cell Surface; D019000:Phosphotyrosine; D014443:Tyrosine; D066246:ErbB Receptors; D017479:Receptors, Platelet-Derived Growth Factor; D010738:Type C Phospholipases; D019204:GTP-Binding Proteins; D002118:Calcium