PMID- 21467038
OWN - NLM
STAT- MEDLINE
DCOM- 20110801
LR  - 20211020
IS  - 1083-351X (Electronic)
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 286
IP  - 22
DP  - 2011 Jun 3
TI  - Ric-8B is a GTP-dependent G protein alphas guanine nucleotide exchange factor.
PG  - 19932-42
LID - 10.1074/jbc.M110.163675 [doi]
AB  - ric-8 (resistance to inhibitors of cholinesterase 8) genes have positive roles in 
      variegated G protein signaling pathways, including Galpha(q) and Galpha(s) regulation of 
      neurotransmission, Galpha(i)-dependent mitotic spindle positioning during 
      (asymmetric) cell division, and Galpha(olf)-dependent odorant receptor signaling. 
      Mammalian Ric-8 activities are partitioned between two genes, ric-8A and ric-8B. 
      Ric-8A is a guanine nucleotide exchange factor (GEF) for Galpha(i)/alpha(q)/alpha(12/13) 
      subunits. Ric-8B potentiated G(s) signaling presumably as a Galpha(s)-class GEF 
      activator, but no demonstration has shown Ric-8B GEF activity. Here, two Ric-8B 
      isoforms were purified and found to be Galpha subunit GDP release factor/GEFs. In 
      HeLa cells, full-length Ric-8B (Ric-8BFL) bound endogenously expressed Galpha(s) and 
      lesser amounts of Galpha(q) and Galpha(13). Ric-8BFL stimulated guanosine 
      5'-3-O-(thio)triphosphate (GTPgammaS) binding to these subunits and Galpha(olf), whereas 
      the Ric-8BDelta9 isoform stimulated Galpha(s short) GTPgammaS binding only. Michaelis-Menten 
      experiments showed that Ric-8BFL elevated the V(max) of Galpha(s) steady state GTP 
      hydrolysis and the apparent K(m) values of GTP binding to Galpha(s) from  approximately 385 nm to 
      an estimated value of  approximately 42 muM. Directionality of the Ric-8BFL-catalyzed Galpha(s) 
      exchange reaction was GTP-dependent. At sub-K(m) GTP, Ric-BFL was inhibitory to 
      exchange despite being a rapid GDP release accelerator. Ric-8BFL binds 
      nucleotide-free Galpha(s) tightly, and near-K(m) GTP levels were required to 
      dissociate the Ric-8B.Galpha nucleotide-free intermediate to release free Ric-8B and 
      Galpha-GTP. Ric-8BFL-catalyzed nucleotide exchange probably proceeds in the forward 
      direction to produce Galpha-GTP in cells.
FAU - Chan, PuiYee
AU  - Chan P
AD  - Department of Pharmacology and Physiology, University of Rochester Medical 
      Center, Rochester, New York 14642, USA.
FAU - Gabay, Meital
AU  - Gabay M
FAU - Wright, Forrest A
AU  - Wright FA
FAU - Tall, Gregory G
AU  - Tall GG
LA  - eng
GR  - R01 GM088242/GM/NIGMS NIH HHS/United States
GR  - T32 DA007232/DA/NIDA NIH HHS/United States
GR  - T32 DA07232/DA/NIDA NIH HHS/United States
GR  - GM088242/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20110405
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (GTP-Binding Protein alpha Subunits)
RN  - 0 (Guanine Nucleotide Exchange Factors)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Protein Isoforms)
RN  - 0 (Ric8a protein, mouse)
RN  - 0 (Ric8b protein, mouse)
RN  - 86-01-1 (Guanosine Triphosphate)
SB  - IM
MH  - Animals
MH  - Catalysis
MH  - Cell Line
MH  - GTP-Binding Protein alpha Subunits/genetics/*metabolism
MH  - Guanine Nucleotide Exchange Factors/genetics/*metabolism
MH  - Guanosine Triphosphate/genetics/*metabolism
MH  - Mice
MH  - Nuclear Proteins/genetics/*metabolism
MH  - Protein Isoforms
MH  - Rats
PMC - PMC3103368
EDAT- 2011/04/07 06:00
MHDA- 2011/08/02 06:00
PMCR- 2012/06/03
CRDT- 2011/04/07 06:00
PHST- 2011/04/07 06:00 [entrez]
PHST- 2011/04/07 06:00 [pubmed]
PHST- 2011/08/02 06:00 [medline]
PHST- 2012/06/03 00:00 [pmc-release]
AID - S0021-9258(20)51067-3 [pii]
AID - M110.163675 [pii]
AID - 10.1074/jbc.M110.163675 [doi]
PST - ppublish
SO  - J Biol Chem. 2011 Jun 3;286(22):19932-42. doi: 10.1074/jbc.M110.163675. Epub 2011 
      Apr 5.