PMID- 11313912
OWN - NLM
STAT- MEDLINE
DCOM- 20010510
LR  - 20131121
IS  - 0950-9232 (Print)
IS  - 0950-9232 (Linking)
VI  - 20
IP  - 13
DP  - 2001 Mar 26
TI  - Regulation of G proteins by covalent modification.
PG  - 1643-52
AB  - Heterotrimeric G protein alpha,beta, and gamma subunits are subject to several 
      kinds of co- and post-translational covalent modifications. Among those relevant 
      to G protein-coupled receptor signaling in normal cell function are lipid 
      modifications and phosphorylation. N-myristoylation is a co-translational 
      modification occurring for members of the G(i) family of Galpha subunits, while 
      palmitoylation is a post-translational modification that occurs for these and 
      most other Galpha subunits. One or both modifications are required for plasma 
      membrane targeting and contribute to regulating strength of interaction with the 
      Gbetagamma heterodimer, effectors, and regulators of G protein signaling (RGS 
      proteins). Galpha subunits, including those with transforming activity, are often 
      inactive when unable to be modified with lipids. The reversible nature of 
      palmitoylation is intriguing in this regard, as it lends itself to a regulation 
      integrated with the activation state of the G protein. Several Galpha subunits 
      are substrates for phosphorylation by protein kinase C and at least one is a 
      substrate for phosphorylation by the p21-activated protein kinase. 
      Phosphorylation in both instances inhibits the interactions of these subunits 
      with the Gbetagamma heterodimer and RGS proteins. Several Galpha subunits are 
      also substrates for tyrosine phosphorylation. A Ggamma subunit is phosphorylated 
      by protein kinase C, with the consequence that it interacts more tightly with a 
      Galpha subunit but less well with an effector.
FAU - Chen, C A
AU  - Chen CA
AD  - Department of Pharmacology, University of Pennsylvania School of Medicine, 3620 
      Hamilton Walk, Philadelphia, PA 19104-6084, USA.
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.
PT  - Review
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (Protein Subunits)
RN  - 0I3V7S25AW (Myristic Acid)
RN  - 2V16EO95H1 (Palmitic Acid)
RN  - EC 3.6.1.- (GTP-Binding Proteins)
SB  - IM
MH  - Acylation
MH  - Cell Membrane/metabolism
MH  - GTP-Binding Proteins/*metabolism
MH  - Myristic Acid/metabolism
MH  - Palmitic Acid/metabolism
MH  - Phosphorylation
MH  - *Protein Processing, Post-Translational
MH  - Protein Subunits
MH  - Protein Transport
RF  - 90
EDAT- 2001/04/21 10:00
MHDA- 2001/05/22 10:01
CRDT- 2001/04/21 10:00
PHST- 2001/04/21 10:00 [pubmed]
PHST- 2001/05/22 10:01 [medline]
PHST- 2001/04/21 10:00 [entrez]
AID - 10.1038/sj.onc.1204185 [doi]
PST - ppublish
SO  - Oncogene. 2001 Mar 26;20(13):1643-52. doi: 10.1038/sj.onc.1204185.