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Published 8 December 2003. doi:10.1083/jcb.200307155
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© The Rockefeller University Press, 0021-9525/2003/12/1157 $8.00
The Journal of Cell Biology, Volume 163, Number 5, 1157-1165


Article

The ubiquitin-related protein PLIC-1 regulates heterotrimeric G protein function through association with Gß{gamma}

Elsa-Noah N'Diaye and Eric J. Brown

Program in Host–Pathogen Interactions, University of California, San Francisco, San Francisco, CA 94143

Address correspondence to Eric J. Brown, Program in Host–Pathogen Interactions, University of California, San Francisco, Campus Box 2140, 600 16th St., San Francisco, CA 94143-2140. Tel.: (415) 514-0167. Fax: (415) 514-0169. email: ebrown{at}medicine.ucsf.edu

PLIC-1, a newly described ubiquitin-related protein, inhibited both Jurkat migration toward SDF-1{alpha} and A431 wound healing, but the closely related PLIC-2 did not. PLIC-1 prevented the SDF-1{alpha}–induced activation of phospholipase C, decreased ligand-induced internalization of SDF-1{alpha} receptor CXCR4 and inhibited chemotaxis signaled by a transfected Gi-coupled receptor. However, PLIC-1 had no effect on Gs-mediated adenylyl cyclase activation, and inhibited only the Gß{gamma}-dependent component of Gq-initiated increase in [Ca2+]i, which is consistent with selective inhibition of {gamma} function. PLIC-1 colocalized with G proteins in lamellae and pseudopods, and precipitated Gß{gamma} in pull downs. Interaction with Gß{gamma} did not require PLIC-1's ubiquitin-like or ubiquitin-associated domains, and proteasome inhibition had no effect on SDF-1{alpha} activation of phospholipase C, indicating that PLIC-1's inhibition of Gß{gamma} did not result from effects on proteasome function. Thus, PLIC-1 inhibits Gi signaling by direct association with Gß{gamma}; because it also interacts with CD47, a modulator of integrin function, it likely has a role integrating adhesion and signaling components of cell migration.

Key Words: cell migration; CD47; chemokines; migration; signal transduction


Abbreviations used in this paper: GPCR, G protein–coupled receptor; Pd, phosducin; PhLP, phosducin-like protein; PTX, pertussis toxin; Uba, ubiquitin-associated; Ubq; ubiquitin-like.


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