Induction of inducible nitric-oxide synthase by the heterotrimeric G protein Gα13

Kenichiro Kitamura, William D. Singer, Robert A. Star, Shmuel Muallem, R. Tyler Miller

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

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 αssQ227L) or were minimally increased in cells expressing activated αi1i1Q204L) and αqqQ209L), 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.

Original languageEnglish (US)
Pages (from-to)7412-7415
Number of pages4
JournalJournal of Biological Chemistry
Volume271
Issue number13
DOIs
StatePublished - Mar 29 1996

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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