PMID- 10608901
OWN - NLM
STAT- MEDLINE
DCOM- 20000208
LR  - 20190508
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 53
DP  - 1999 Dec 31
TI  - Palmitoylation of a conserved cysteine in the regulator of G protein signaling
      (RGS) domain modulates the GTPase-activating activity of RGS4 and RGS10.
PG  - 38260-7
AB  - RGS4 and RGS10 expressed in Sf9 cells are palmitoylated at a conserved Cys
      residue (Cys(95) in RGS4, Cys(66) in RGS10) in the regulator of G protein
      signaling (RGS) domain that is also autopalmitoylated when the purified proteins 
      are incubated with palmitoyl-CoA. RGS4 also autopalmitoylates at a previously
      identified cellular palmitoylation site, either Cys(2) or Cys(12). The C2A/C12A
      mutation essentially eliminates both autopalmitoylation and cellular
      [(3)H]palmitate labeling of Cys(95). Membrane-bound RGS4 is palmitoylated both at
      Cys(95) and Cys(2/12), but cytosolic RGS4 is not palmitoylated. RGS4 and RGS10
      are GTPase-activating proteins (GAPs) for the G(i) and G(q) families of G
      proteins. Palmitoylation of Cys(95) on RGS4 or Cys(66) on RGS10 inhibits GAP
      activity 80-100% toward either Galpha(i) or Galpha(z) in a single-turnover,
      solution-based assay. In contrast, when GAP activity was assayed as acceleration 
      of steady-state GTPase in receptor-G protein proteoliposomes, palmitoylation of
      RGS10 potentiated GAP activity >/=20-fold. Palmitoylation near the N terminus of 
      C95V RGS4 did not alter GAP activity toward soluble Galpha(z) and increased G(z) 
      GAP activity about 2-fold in the vesicle-based assay. Dual palmitoylation of
      wild-type RGS4 remained inhibitory. RGS protein palmitoylation is thus
      multi-site, complex in its control, and either inhibitory or stimulatory
      depending on the RGS protein and its sites of palmitoylation.
FAU - Tu, Y
AU  - Tu Y
AD  - Department of Pharmacology, University of Texas Southwestern Medical Center,
      Dallas, Texas 75390-9041, USA.
FAU - Popov, S
AU  - Popov S
FAU - Slaughter, C
AU  - Slaughter C
FAU - Ross, E M
AU  - Ross EM
LA  - eng
GR  - GM30355/GM/NIGMS 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  - 0 (DNA, Complementary)
RN  - 0 (GTPase-Activating Proteins)
RN  - 0 (RGS Proteins)
RN  - 0 (RGS10 protein, human)
RN  - 175335-35-0 (RGS4 protein)
RN  - 2V16EO95H1 (Palmitic Acid)
RN  - EC 3.6.1.- (GTP-Binding Proteins)
RN  - K848JZ4886 (Cysteine)
SB  - IM
MH  - Animals
MH  - Base Sequence
MH  - Cysteine/chemistry/*metabolism
MH  - DNA Primers
MH  - DNA, Complementary
MH  - GTP-Binding Proteins/chemistry/*metabolism
MH  - GTPase-Activating Proteins/chemistry/genetics/*metabolism
MH  - Mutagenesis, Site-Directed
MH  - Palmitic Acid/*metabolism
MH  - RGS Proteins/chemistry/genetics/*metabolism
MH  - Spodoptera
EDAT- 1999/12/23 00:00
MHDA- 1999/12/23 00:01
CRDT- 1999/12/23 00:00
PHST- 1999/12/23 00:00 [pubmed]
PHST- 1999/12/23 00:01 [medline]
PHST- 1999/12/23 00:00 [entrez]
AID - 10.1074/jbc.274.53.38260 [doi]
PST - ppublish
SO  - J Biol Chem. 1999 Dec 31;274(53):38260-7. doi: 10.1074/jbc.274.53.38260.