TY - JOUR
T1 - Induction of inducible nitric-oxide synthase by the heterotrimeric G protein Gα13
AU - Kitamura, Kenichiro
AU - Singer, William D.
AU - Star, Robert A.
AU - Muallem, Shmuel
AU - Miller, R. Tyler
PY - 1996/3/29
Y1 - 1996/3/29
N2 - While the functions of several G protein α subunits such as αs and αq are relatively well understood, the action of others such as α13 remain largely undefined. Because of recent interest in regulation of nitric-oxide synthase (NOS) by G protein-coupled signaling systems and findings that receptors for two proinflammatory substances, thrombin and thromboxane couple to α13, we studied the effect of α13 on NOS activity in a renal epithelial cell line. We found that stable overexpression of α13 or its GTPase-deficient mutant, α13Q226L, in a continuous renal epithelial cell line (MCT) increased NOS activity. The increased NOS activity was due to increased expression of the macrophage-inducible form of NOS (iNOS). iNOS protein and activity were not increased in similar cells expressing an activated αs (αsQ227L) or were minimally increased in cells expressing activated αi1 (αi1Q204L) and αq (αqQ209L), members of the three other G protein a chain families. Transient co-expression of α13 or α13Q226L increased the activity of an iNOS promoter-CAT construct demonstrating that α13 increases iNOS expression through transcription. Consequently, α13 induces iNOS through a novel mechanism that is distinct from that of other G protein a chains and that may mediate the actions of G protein-dependent proinflammatory agents.
AB - While the functions of several G protein α subunits such as αs and αq are relatively well understood, the action of others such as α13 remain largely undefined. Because of recent interest in regulation of nitric-oxide synthase (NOS) by G protein-coupled signaling systems and findings that receptors for two proinflammatory substances, thrombin and thromboxane couple to α13, we studied the effect of α13 on NOS activity in a renal epithelial cell line. We found that stable overexpression of α13 or its GTPase-deficient mutant, α13Q226L, in a continuous renal epithelial cell line (MCT) increased NOS activity. The increased NOS activity was due to increased expression of the macrophage-inducible form of NOS (iNOS). iNOS protein and activity were not increased in similar cells expressing an activated αs (αsQ227L) or were minimally increased in cells expressing activated αi1 (αi1Q204L) and αq (αqQ209L), members of the three other G protein a chain families. Transient co-expression of α13 or α13Q226L increased the activity of an iNOS promoter-CAT construct demonstrating that α13 increases iNOS expression through transcription. Consequently, α13 induces iNOS through a novel mechanism that is distinct from that of other G protein a chains and that may mediate the actions of G protein-dependent proinflammatory agents.
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U2 - 10.1074/jbc.271.13.7412
DO - 10.1074/jbc.271.13.7412
M3 - Article
C2 - 8631766
AN - SCOPUS:0029887624
SN - 0021-9258
VL - 271
SP - 7412
EP - 7415
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 13
ER -