TY - JOUR
T1 - Regulation of the M1 muscarinic receptor-Gg-phospholipase C-β pathway by nucleotide exchange and GTP hydrolysis
AU - Ross, Elliott M.
AU - Berstein, Gabriel
N1 - Funding Information:
The work described here was the product of three crucial collaborations: with Alan Smrcka and Paul Sternweis in this department, with Jonathan Blank and John Exton at the Howard Hughes Medical Institute and Vanderbilt University, and with Dock-Young Jhon, Dongeun Park and Sue Goo Rhee at the National Heart, Lung and Blood Institute. Experiments performed in our laboratory were supported by NIH grant R37GM30355, NIH Fogarty International Fellowship $32GM14489 and R.A. Welch Foundation grant 1-0982.
PY - 1993
Y1 - 1993
N2 - M1 muscarinic choligernic receptor, Gq and G11 (G q 11), and phospholipase C-β1 were highly purified from both natural sources and cells that express the appropriate cDNA's. When the proteins were co-reconstituted in into phospholipid vesicles, the receptor efficiently and selectively promoted the activation of if G q 11, leading to marked stimulation of PLC activity in the presence of GTPγS. No stimulation was observed in the presence of GTP, however, which led to the finding that PLC-β1 stimulates the hydrolysis of if G q 11-bound GTP at leasr 50-fold. Thus, PLC-β1 is a GTPase activating protein, a GAP, for its physiologic regulator G in q 11. We discuss the implications of PLC- β1's GAP activity on the M1 muscarinic cholinergic signaling pathway.
AB - M1 muscarinic choligernic receptor, Gq and G11 (G q 11), and phospholipase C-β1 were highly purified from both natural sources and cells that express the appropriate cDNA's. When the proteins were co-reconstituted in into phospholipid vesicles, the receptor efficiently and selectively promoted the activation of if G q 11, leading to marked stimulation of PLC activity in the presence of GTPγS. No stimulation was observed in the presence of GTP, however, which led to the finding that PLC-β1 stimulates the hydrolysis of if G q 11-bound GTP at leasr 50-fold. Thus, PLC-β1 is a GTPase activating protein, a GAP, for its physiologic regulator G in q 11. We discuss the implications of PLC- β1's GAP activity on the M1 muscarinic cholinergic signaling pathway.
UR - http://www.scopus.com/inward/record.url?scp=0027446305&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0027446305&partnerID=8YFLogxK
U2 - 10.1016/0024-3205(93)90296-F
DO - 10.1016/0024-3205(93)90296-F
M3 - Article
C2 - 8441322
AN - SCOPUS:0027446305
VL - 52
SP - 413
EP - 419
JO - Life Sciences
JF - Life Sciences
SN - 0024-3205
IS - 5-6
ER -