PMID- 10488065
OWN - NLM
STAT- MEDLINE
DCOM- 19991104
LR  - 20190508
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 39
DP  - 1999 Sep 24
TI  - Differential coupling of the sphingosine 1-phosphate receptors Edg-1, Edg-3, and 
      H218/Edg-5 to the G(i), G(q), and G(12) families of heterotrimeric G proteins.
PG  - 27351-8
AB  - Sphingosine 1-phosphate (S1P) is one of several bioactive phospholipids that
      exert profound mitogenic and morphogenic actions. Originally characterized as a
      second messenger, S1P is now recognized to achieve many of its effects through
      cell surface, G protein-coupled receptors. We used a subunit-selective
      [(35)S]GTPgammaS binding assay to investigate whether the variety of actions
      exerted through Edg-1, a recently identified receptor for S1P, might be achieved 
      through multiple G proteins. We found, employing both Sf9 and HEK293 cells, that 
      Edg-1 activates only members of the G(i) family, and not G(s), G(q), G(12), or
      G(13). We additionally established that Edg-1 activates G(i) in response not only
      to S1P but also sphingosylphosphorylcholine; no effects of lysophosphatidic acid 
      through Edg-1 were evident. Our assays further revealed a receptor(s) for S1P
      endogenous to HEK293 cells that mediates activation of G(13) as well as G(i).
      Because several of the biological actions of S1P are assumed to proceed through
      the G(12/13) family, we tested whether Edg-3 and H218/Edg-5, two other receptors 
      for S1P, might have a broader coupling profile than Edg-1. Indeed, Edg-3 and
      H218/Edg-5 communicate not only with G(i) but also with G(q) and G(13). These
      studies represent the first characterization of S1P receptor activity through G
      proteins directly and establish fundamental differences in coupling.
FAU - Windh, R T
AU  - Windh RT
AD  - Department of Pharmacology, University of Pennsylvania School of Medicine,
      Philadelphia, Pennsylvania 19104, USA.
FAU - Lee, M J
AU  - Lee MJ
FAU - Hla, T
AU  - Hla T
FAU - An, S
AU  - An S
FAU - Barr, A J
AU  - Barr AJ
FAU - Manning, D R
AU  - Manning DR
LA  - eng
GR  - GM51196/GM/NIGMS NIH HHS/United States
PT  - Journal Article
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-Binding Proteins)
RN  - 0 (I-kappa B Proteins)
RN  - 0 (Immediate-Early Proteins)
RN  - 0 (Lysophospholipids)
RN  - 0 (Macromolecular Substances)
RN  - 0 (NFKBIA protein, human)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (Receptors, G-Protein-Coupled)
RN  - 0 (Receptors, Lysophospholipid)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Sulfur Radioisotopes)
RN  - 0 (Virulence Factors, Bordetella)
RN  - 139874-52-5 (NF-KappaB Inhibitor alpha)
RN  - 26993-30-6 (sphingosine 1-phosphate)
RN  - 37589-80-3 (Guanosine 5'-O-(3-Thiotriphosphate))
RN  - EC 3.6.1.- (GTP-Binding Proteins)
RN  - NGZ37HRE42 (Sphingosine)
SB  - IM
MH  - Animals
MH  - Cell Line
MH  - DNA-Binding Proteins/*metabolism
MH  - GTP-Binding Proteins/*metabolism
MH  - Guanosine 5'-O-(3-Thiotriphosphate)/metabolism
MH  - Humans
MH  - *I-kappa B Proteins
MH  - Immediate-Early Proteins/*metabolism
MH  - Kinetics
MH  - *Lysophospholipids
MH  - Macromolecular Substances
MH  - NF-KappaB Inhibitor alpha
MH  - Receptors, Cell Surface/*metabolism
MH  - *Receptors, G-Protein-Coupled
MH  - Receptors, Lysophospholipid
MH  - Recombinant Proteins/metabolism
MH  - Sphingosine/*analogs & derivatives/metabolism
MH  - Spodoptera
MH  - Sulfur Radioisotopes
MH  - Transfection
MH  - Virulence Factors, Bordetella/pharmacology
EDAT- 1999/09/17 00:00
MHDA- 1999/09/17 00:01
CRDT- 1999/09/17 00:00
PHST- 1999/09/17 00:00 [pubmed]
PHST- 1999/09/17 00:01 [medline]
PHST- 1999/09/17 00:00 [entrez]
AID - 10.1074/jbc.274.39.27351 [doi]
PST - ppublish
SO  - J Biol Chem. 1999 Sep 24;274(39):27351-8. doi: 10.1074/jbc.274.39.27351.