TY - JOUR
T1 - Protein kinase C alters the responsiveness of adenylyl cyclases to G protein α and βγ subunits
AU - Zimmermann, Gregor
AU - Taussig, Ronald
PY - 1996
Y1 - 1996
N2 - The ability of protein kinase C (PKC) to regulate the responsiveness of adenylyl cyclase to different activators was assessed. Membranes prepared from Sf9 cells infected with recombinant baculoviruses encoding either type II or IV adenylyl cyclase were incubated with recombinant PKCα (purified from Sf9 cells), and the effects on adenylyl cyclase activity were measured after reconstitution with G(sα), Gβγ, or forskolin. PKCα treatment of type II adenylyl cyclase leads to increases in basal, forskolin-stimulated, and βγ-stimulated activities and greater sensitivity to stimulation by G(sα). Paradoxically, most of the βγ potentiation of G(sα)-stimulated activity is eliminated by pretreatment with PKCα. By contrast, treatment of type IV adenylyl cyclase with PKCα has little effect on the basal, forskolin-stimulated, or βγ-stimulated activities but markedly reduces the G(sα)stimulated and βγ-potentiated activity of this isoform. These studies demonstrate that protein kinases can alter both the activity of adenylyl cyclase isoforms and their responsiveness to G protein regulation, thereby altering the ability of adenylyl cyclases to integrate signals derived from multiple hormonal inputs.
AB - The ability of protein kinase C (PKC) to regulate the responsiveness of adenylyl cyclase to different activators was assessed. Membranes prepared from Sf9 cells infected with recombinant baculoviruses encoding either type II or IV adenylyl cyclase were incubated with recombinant PKCα (purified from Sf9 cells), and the effects on adenylyl cyclase activity were measured after reconstitution with G(sα), Gβγ, or forskolin. PKCα treatment of type II adenylyl cyclase leads to increases in basal, forskolin-stimulated, and βγ-stimulated activities and greater sensitivity to stimulation by G(sα). Paradoxically, most of the βγ potentiation of G(sα)-stimulated activity is eliminated by pretreatment with PKCα. By contrast, treatment of type IV adenylyl cyclase with PKCα has little effect on the basal, forskolin-stimulated, or βγ-stimulated activities but markedly reduces the G(sα)stimulated and βγ-potentiated activity of this isoform. These studies demonstrate that protein kinases can alter both the activity of adenylyl cyclase isoforms and their responsiveness to G protein regulation, thereby altering the ability of adenylyl cyclases to integrate signals derived from multiple hormonal inputs.
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U2 - 10.1074/jbc.271.43.27161
DO - 10.1074/jbc.271.43.27161
M3 - Article
C2 - 8900209
AN - SCOPUS:0029998598
SN - 0021-9258
VL - 271
SP - 27161
EP - 27166
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 43
ER -