PMID- 8631766
OWN - NLM
STAT- MEDLINE
DCOM- 19960703
LR  - 20210210
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 271
IP  - 13
DP  - 1996 Mar 29
TI  - Induction of inducible nitric-oxide synthase by the heterotrimeric G protein 
      Galpha13.
PG  - 7412-5
AB  - While the functions of several G protein alpha subunits such as alpha(s( and 
      alpha(q) are relatively well understood, the action of others such as alpha13 
      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 alpha13, we studied the effect of alpha13 on NOS activity in a renal 
      epithelial cell line. We found that stable overexpression of alpha13 or its 
      GTPase-deficient mutant, alpha13Q226L, 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 alpha(s) 
      (alpha(s)Q227L) or were minimally increased in cells expressing activated 
      alpha(i1) (alpha-i1Q204L) and alpha(q) (alpha(q)Q209L), members of the three 
      other G protein alpha chain families. Transient co-expression of alpha13 or 
      alpha13Q226L increased the activity of an iNOS promoter-CAT construct 
      demonstrating that alpha13 increases iNOS expression through transcription. 
      Consequently, alpha13 induces iNOS through a novel mechanism that is distinct 
      from that of other G protein alpha chains and that may mediate the actions of G 
      protein-dependent proinflammatory agents.
FAU - Kitamura, K
AU  - Kitamura K
AD  - Department of Medicine, University of Florida, Gainesville, 32610, USA.
FAU - Singer, W D
AU  - Singer WD
FAU - Star, R A
AU  - Star RA
FAU - Muallem, S
AU  - Muallem S
FAU - Miller, R T
AU  - Miller RT
LA  - eng
GR  - DK39298/DK/NIDDK NIH HHS/United States
GR  - F32-GM15359/GM/NIGMS NIH HHS/United States
GR  - R29DK41726/DK/NIDDK NIH HHS/United States
GR  - etc.
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (DNA, Complementary)
RN  - 0 (Isoenzymes)
RN  - 0 (Macromolecular Substances)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Recombinant Proteins)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase)
RN  - EC 2.3.1.28 (Chloramphenicol O-Acetyltransferase)
RN  - EC 3.6.1.- (GTP-Binding Proteins)
SB  - IM
MH  - Animals
MH  - Cell Line
MH  - Chloramphenicol O-Acetyltransferase/biosynthesis
MH  - DNA, Complementary
MH  - Enzyme Induction
MH  - GTP-Binding Proteins/chemistry/*metabolism
MH  - Gene Expression Regulation, Enzymologic
MH  - Immunoblotting
MH  - Isoenzymes/biosynthesis
MH  - Kidney Tubules, Proximal
MH  - Kinetics
MH  - Macromolecular Substances
MH  - Mice
MH  - Nitric Oxide Synthase/*biosynthesis/metabolism
MH  - Promoter Regions, Genetic
MH  - Recombinant Fusion Proteins/biosynthesis/metabolism
MH  - Recombinant Proteins/chemistry/metabolism
MH  - Signal Transduction
MH  - Transfection
EDAT- 1996/03/29 00:00
MHDA- 1996/03/29 00:01
CRDT- 1996/03/29 00:00
PHST- 1996/03/29 00:00 [pubmed]
PHST- 1996/03/29 00:01 [medline]
PHST- 1996/03/29 00:00 [entrez]
AID - S0021-9258(17)45137-4 [pii]
AID - 10.1074/jbc.271.13.7412 [doi]
PST - ppublish
SO  - J Biol Chem. 1996 Mar 29;271(13):7412-5. doi: 10.1074/jbc.271.13.7412.