PMID- 8602223
OWN - NLM
STAT- MEDLINE
DCOM- 19960503
LR  - 20091119
IS  - 0028-0836 (Print)
IS  - 0028-0836 (Linking)
VI  - 379
IP  - 6567
DP  - 1996 Feb 22
TI  - Inhibition of G-protein-mediated MAP kinase activation by a new mammalian gene 
      family.
PG  - 742-6
AB  - A general property of signal transduction pathways is that prolonged stimulation 
      decreases responsiveness, a phenomenon termed desensitization. Yeast cells 
      stimulated with mating pheromone activate a heterotrimeric G-protein-linked, 
      MAP-kinase-dependent signalling pathway that induces G1-phase cell-cycle arrest 
      and morphological differentiation (reviewed in refs 1, 2). Eventually the cells 
      desensitize to pheromone and resume growth. Genetic studies have demonstrated the 
      relative importance of a desensitization mechanism that uses the SST2 gene 
      product, Sst2p. Here we identify a mammalian gene family termed RGS (for 
      regulator of G-protein signalling) that encodes structural and functional 
      homologues of Sst2p. Introduction of RGS family members into yeast blunts signal 
      transduction through the pheromone-response pathway. Like SST2 (refs 8-10), they 
      negatively regulate this pathway at a point upstream or at the level of the G 
      protein. The RGS family members also markedly impair MAP kinase activation by 
      mammalian G-protein-linked receptors, indicating the existence and importance of 
      an SST2-like desensitization mechanism in mammalian cells.
FAU - Druey, K M
AU  - Druey KM
AD  - Laboratory of Immunoregulation, National Institute of Allergy and Infectious 
      Diseases, National Institutes of Health, Bethesda, Maryland 20892-1876, USA.
FAU - Blumer, K J
AU  - Blumer KJ
FAU - Kang, V H
AU  - Kang VH
FAU - Kehrl, J H
AU  - Kehrl JH
LA  - eng
SI  - GENBANK/U27655
SI  - GENBANK/U27767
SI  - GENBANK/U27768
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Nature
JT  - Nature
JID - 0410462
RN  - 0 (Antigens, CD)
RN  - 0 (DNA Probes)
RN  - 0 (Fungal Proteins)
RN  - 0 (GTPase-Activating Proteins)
RN  - 0 (Pheromones)
RN  - 0 (Proteins)
RN  - 0 (RGS Proteins)
RN  - 0 (RGS3 protein, human)
RN  - 0 (Receptors, Interleukin)
RN  - 0 (Receptors, Interleukin-8A)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Repressor Proteins)
RN  - 0 (Rgs3 protein, mouse)
RN  - 0 (Rgs3 protein, rat)
RN  - 0 (SST2 protein, S cerevisiae)
RN  - 0 (Saccharomyces cerevisiae Proteins)
RN  - 175335-35-0 (RGS4 protein)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 3.6.1.- (GTP-Binding Proteins)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Antigens, CD/metabolism
MH  - Base Sequence
MH  - Calcium-Calmodulin-Dependent Protein Kinases/*antagonists & inhibitors/metabolism
MH  - Cell Line
MH  - DNA Probes
MH  - Enzyme Activation
MH  - Fungal Proteins/genetics
MH  - GTP-Binding Proteins/antagonists & inhibitors/*metabolism
MH  - *GTPase-Activating Proteins
MH  - Humans
MH  - Mitogen-Activated Protein Kinase 3
MH  - *Mitogen-Activated Protein Kinases
MH  - Molecular Sequence Data
MH  - *Multigene Family
MH  - Pheromones/metabolism
MH  - Proteins/genetics/*metabolism
MH  - *RGS Proteins
MH  - Rats
MH  - Receptors, Interleukin/metabolism
MH  - Receptors, Interleukin-8A
MH  - Recombinant Proteins/metabolism
MH  - *Repressor Proteins
MH  - *Saccharomyces cerevisiae Proteins
MH  - Sequence Alignment
MH  - Signal Transduction
EDAT- 1996/02/22 00:00
MHDA- 1996/02/22 00:01
CRDT- 1996/02/22 00:00
PHST- 1996/02/22 00:00 [pubmed]
PHST- 1996/02/22 00:01 [medline]
PHST- 1996/02/22 00:00 [entrez]
AID - 10.1038/379742a0 [doi]
PST - ppublish
SO  - Nature. 1996 Feb 22;379(6567):742-6. doi: 10.1038/379742a0.