PMID- 9436987
OWN - NLM
STAT- MEDLINE
DCOM- 19980310
LR  - 20190607
IS  - 1059-1524 (Print)
IS  - 1059-1524 (Linking)
VI  - 9
IP  - 1
DP  - 1998 Jan
TI  - Plasma membrane localization of G alpha z requires two signals.
PG  - 1-14
AB  - Three covalent attachments anchor heterotrimeric G proteins to cellular 
      membranes: the alpha subunits are myristoylated and/or palmitoylated, whereas the 
      gamma chain is prenylated. Despite the essential role of these modifications in 
      membrane attachment, it is not clear how they cooperate to specify G protein 
      localization at the plasma membrane, where the G protein relays signals from cell 
      surface receptors to intracellular effector molecules. To explore this question, 
      we studied the effects of mutations that prevent myristoylation and/or 
      palmitoylation of an epitope-labeled alpha subunit, alpha z. Wild-type alpha z 
      (alpha z-WT) localizes specifically at the plasma membrane. A mutant that 
      incorporates only myristate is mistargeted to intracellular membranes, in 
      addition to the plasma membrane, but transduces hormonal signals as well as does 
      alpha z-WT. Removal of the myristoylation site produced a mutant alpha z that is 
      located in the cytosol, is not efficiently palmitoylated, and does not relay the 
      hormonal signal. Coexpression of beta gamma with this myristoylation defective 
      mutant transfers it to the plasma membrane, promotes its palmitoylation, and 
      enables it to transmit hormonal signals. Pulse-chase experiments show that the 
      palmitate attached to this myristoylation-defective mutant turns over much more 
      rapidly than does palmitate on alpha z-WT, and that the rate of turnover is 
      further accelerated by receptor activation. In contrast, receptor activation does 
      not increase the slow rate of palmitate turnover on alpha z-WT. Together these 
      results suggest that myristate and beta gamma promote stable association with 
      membranes not only by providing hydrophobicity, but also by stabilizing 
      attachment of palmitate. Moreover, palmitoylation confers on alpha z specific 
      localization at the plasma membrane.
FAU - Morales, J
AU  - Morales J
AD  - Department of Cellular and Molecular Pharmacology, University of California, San 
      Francisco, California 94143, USA.
FAU - Fishburn, C S
AU  - Fishburn CS
FAU - Wilson, P T
AU  - Wilson PT
FAU - Bourne, H R
AU  - Bourne HR
LA  - eng
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  - Mol Biol Cell
JT  - Molecular biology of the cell
JID - 9201390
RN  - 0 (GTP-Binding Protein alpha Subunits)
RN  - 0 (Palmitates)
RN  - 0I3V7S25AW (Myristic Acid)
RN  - EC 3.6.1.- (GTP-Binding Proteins)
RN  - EC 3.6.5.1 (Heterotrimeric GTP-Binding Proteins)
SB  - IM
MH  - Animals
MH  - Binding Sites
MH  - CHO Cells
MH  - Cell Membrane/metabolism/physiology
MH  - Cricetinae
MH  - *GTP-Binding Protein alpha Subunits
MH  - GTP-Binding Proteins/genetics/*metabolism/*physiology
MH  - *Heterotrimeric GTP-Binding Proteins
MH  - Microscopy, Fluorescence
MH  - Myristic Acid/metabolism
MH  - Palmitates/metabolism
MH  - *Signal Transduction
PMC - PMC25209
EDAT- 1998/03/14 00:00
MHDA- 1998/03/14 00:01
CRDT- 1998/03/14 00:00
PHST- 1998/03/14 00:00 [pubmed]
PHST- 1998/03/14 00:01 [medline]
PHST- 1998/03/14 00:00 [entrez]
AID - 10.1091/mbc.9.1.1 [doi]
PST - ppublish
SO  - Mol Biol Cell. 1998 Jan;9(1):1-14. doi: 10.1091/mbc.9.1.1.