PMID- 10559191
OWN - NLM
STAT- MEDLINE
DCOM- 19991214
LR  - 20190508
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 47
DP  - 1999 Nov 19
TI  - Receptor-independent activators of heterotrimeric G-protein signaling pathways.
PG  - 33202-5
AB  - Heterotrimeric G-protein signaling systems are activated via cell surface
      receptors possessing the seven-membrane span motif. Several observations suggest 
      the existence of other modes of stimulus input to heterotrimeric G-proteins. As
      part of an overall effort to identify such proteins we developed a functional
      screen based upon the pheromone response pathway in Saccharomyces cerevisiae. We 
      identified two mammalian proteins, AGS2 and AGS3 (activators of G-protein
      signaling), that activated the pheromone response pathway at the level of
      heterotrimeric G-proteins in the absence of a typical receptor.
      beta-galactosidase reporter assays in yeast strains expressing different Galpha
      subunits (Gpa1, G(s)alpha, G(i)alpha(2(Gpa1(1-41))), G(i)alpha(3(Gpa1(1-41))),
      Galpha(16(Gpa1(1-41)))) indicated that AGS proteins selectively activated
      G-protein heterotrimers. AGS3 was only active in the G(i)alpha(2) and
      G(i)alpha(3) genetic backgrounds, whereas AGS2 was active in each of the genetic 
      backgrounds except Gpa1. In protein interaction studies, AGS2 selectively
      associated with Gbetagamma, whereas AGS3 bound Galpha and exhibited a preference 
      for GalphaGDP versus GalphaGTPgammaS. Subsequent studies indicated that the
      mechanisms of G-protein activation by AGS2 and AGS3 were distinct from that of a 
      typical G-protein-coupled receptor. AGS proteins provide unexpected mechanisms
      for input to heterotrimeric G-protein signaling pathways. AGS2 and AGS3 may also 
      serve as novel binding partners for Galpha and Gbetagamma that allow the subunits
      to subserve functions that do not require initial heterotrimer formation.
FAU - Takesono, A
AU  - Takesono A
AD  - Department of Pharmacology, Medical University of South Carolina, Charleston,
      South Carolina 29425, USA.
FAU - Cismowski, M J
AU  - Cismowski MJ
FAU - Ribas, C
AU  - Ribas C
FAU - Bernard, M
AU  - Bernard M
FAU - Chung, P
AU  - Chung P
FAU - Hazard, S 3rd
AU  - Hazard S 3rd
FAU - Duzic, E
AU  - Duzic E
FAU - Lanier, S M
AU  - Lanier SM
LA  - eng
SI  - GENBANK/AF107723
GR  - R01-NS24821/NS/NINDS NIH HHS/United States
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 Primers)
RN  - EC 3.6.5.1 (Heterotrimeric GTP-Binding Proteins)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Base Sequence
MH  - DNA Primers
MH  - Heterotrimeric GTP-Binding Proteins/*metabolism
MH  - Molecular Sequence Data
MH  - Rats
MH  - Saccharomyces cerevisiae/genetics
MH  - Sequence Homology, Amino Acid
MH  - *Signal Transduction
EDAT- 1999/11/24 09:00
MHDA- 2001/03/28 10:01
CRDT- 1999/11/24 09:00
PHST- 1999/11/24 09:00 [pubmed]
PHST- 2001/03/28 10:01 [medline]
PHST- 1999/11/24 09:00 [entrez]
AID - 10.1074/jbc.274.47.33202 [doi]
PST - ppublish
SO  - J Biol Chem. 1999 Nov 19;274(47):33202-5. doi: 10.1074/jbc.274.47.33202.