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J Biol Chem, Vol. 275, Issue 2, 1327-1336, January 14, 2000
From the Department of Microbiology and Immunology and Kimmel
Cancer Institute, Thomas Jefferson University,
Philadelphia, Pennsylvania 19107
Peripheral membrane proteins utilize a variety of
mechanisms to attach tightly, and often reversibly, to cellular
membranes. The covalent lipid modifications, myristoylation and
palmitoylation, are critical for plasma membrane localization of
heterotrimeric G protein
Interaction with G
Is Required for Membrane Targeting and
Palmitoylation of G
s and Gq*
subunits. For s and
q, two subunits that are palmitoylated but not
myristoylated, we examined the importance of interacting with the G
protein 
dimer for their proper plasma membrane localization and
palmitoylation. Conserved subunit N-terminal amino acids predicted
to mediate binding to were mutated to create a series of
binding region mutants expressed in HEK293 cells. These s and q mutants were found in soluble
rather than particulate fractions, and they no longer localized to
plasma membranes as demonstrated by immunofluorescence microscopy. The
mutations also inhibited incorporation of radiolabeled palmitate into
the proteins and abrogated their signaling ability. Additional
q mutants, which contain these mutations but are
modified by both myristate and palmitate, retained their localization
to plasma membranes and ability to undergo palmitoylation. These
findings identify binding to as a critical membrane attachment
signal for s and q and as a prerequisite
for their palmitoylation, while myristoylation can restore membrane
localization and palmitoylation of binding-deficient q subunits.
*
This work was supported in part by a James A. Shannon
Director's award and Grant GM56444 from the National Institutes of
Health (to P. B. W.).The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Pew Scholar in the Biomedical Sciences. To whom correspondence
should be addressed: Dept. of Microbiology and Immunology, Kimmel
Cancer Inst., Thomas Jefferson University, 233 S. 10th St., 839 BLSB,
Philadelphia, PA 19107. Tel.: 215-503-3137; Fax: 215-923-2117; E-mail:
p_wedegaertner@lac.jci.tju.edu.
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