PMID- 10419452
OWN - NLM
STAT- MEDLINE
DCOM- 19990819
LR  - 20190508
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 31
DP  - 1999 Jul 30
TI  - Modulation of rap activity by direct interaction of Galpha(o) with Rap1
      GTPase-activating protein.
PG  - 21507-10
AB  - We used the yeast two-hybrid system to identify proteins that interact directly
      with Galpha(o). Mutant-activated Galpha(o) was used as the bait to screen a cDNA 
      library from chick dorsal root ganglion neurons. We found that Galpha(o)
      interacted with several proteins including Gz-GTPase-activating protein (Gz-GAP),
      a new RGS protein (RGS-17), a novel protein of unknown function (IP6), and
      Rap1GAP. This study focuses on Rap1GAP, which selectively interacts with
      Galpha(o) and Galpha(i) but not with Galpha(s) or Galpha(q). Rap1GAP interacts
      more avidly with the unactivated Galpha(o) as compared with the mutant
      (Q205L)-activated Galpha(o). When expressed in HEK-293 cells, unactivated
      Galpha(o) co-immunoprecipitates with the Rap1GAP. Expression of chick Rap1GAP in 
      PC-12 cells inhibited activation of Rap1 by forskolin. When unactivated Galpha(o)
      was expressed, the amount of activated Rap1 was greatly increased. This effect
      was not observed with the Q205L-Galpha(o). Expression of unactivated Galpha(o)
      stimulated MAP-kinase (MAPK1/2) activity in a Rap1GAP-dependent manner. These
      results identify a novel function of Galpha(o), which in its resting state can
      sequester Rap1GAP thereby regulating Rap1 activity and consequently gating signal
      flow from Rap1 to MAPK1/2. Thus, activation of G(o) could modulate the Rap1
      effects on a variety of cellular functions.
FAU - Jordan, J D
AU  - Jordan JD
AD  - Department of Pharmacology, Mount Sinai School of Medicine, New York, New York
      10029, USA.
FAU - Carey, K D
AU  - Carey KD
FAU - Stork, P J
AU  - Stork PJ
FAU - Iyengar, R
AU  - Iyengar R
LA  - eng
SI  - GENBANK/AF151734
SI  - GENBANK/AF151966
SI  - GENBANK/AF151967
SI  - GENBANK/AF151968
GR  - CA-72971/CA/NCI NIH HHS/United States
GR  - DK-38671/DK/NIDDK NIH HHS/United States
GR  - GM-54508/GM/NIGMS NIH HHS/United States
GR  - etc.
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 (GTPase-Activating Proteins)
RN  - 0 (Proteins)
RN  - 0 (Recombinant Proteins)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases)
RN  - EC 3.6.1.- (GTP-Binding Proteins)
SB  - IM
MH  - Amino Acid Substitution
MH  - Animals
MH  - Calcium-Calmodulin-Dependent Protein Kinases/*metabolism
MH  - Cell Line
MH  - Chickens
MH  - GTP-Binding Proteins/*metabolism
MH  - GTPase-Activating Proteins
MH  - Ganglia, Spinal/*metabolism
MH  - Gene Library
MH  - Humans
MH  - Molecular Sequence Data
MH  - Mutagenesis, Site-Directed
MH  - Neurons/*metabolism
MH  - PC12 Cells
MH  - Proteins/*metabolism
MH  - Rats
MH  - Recombinant Proteins/metabolism
MH  - Transfection
EDAT- 1999/07/27 00:00
MHDA- 1999/07/27 00:01
CRDT- 1999/07/27 00:00
PHST- 1999/07/27 00:00 [pubmed]
PHST- 1999/07/27 00:01 [medline]
PHST- 1999/07/27 00:00 [entrez]
AID - 10.1074/jbc.274.31.21507 [doi]
PST - ppublish
SO  - J Biol Chem. 1999 Jul 30;274(31):21507-10. doi: 10.1074/jbc.274.31.21507.