The ubiquitin-related protein PLIC-1 regulates heterotrimeric G protein function through association with Gbetagamma.

PLIC-1, a newly described ubiquitin-related protein, inhibited both Jurkat migration toward SDF-1alpha and A431 wound healing, but the closely related PLIC-2 did not. PLIC-1 prevented the SDF-1alpha-induced activation of phospholipase C, decreased ligand-induced internalization of SDF-1alpha 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 Gbetagamma-dependent component of Gq-initiated increase in [Ca2+]i, which is consistent with selective inhibition of Gbetagamma function. PLIC-1 colocalized with G proteins in lamellae and pseudopods, and precipitated Gbetagamma in pull downs. Interaction with Gbetagamma did not require PLIC-1's ubiquitin-like or ubiquitin-associated domains, and proteasome inhibition had no effect on SDF-1alpha activation of phospholipase C, indicating that PLIC-1's inhibition of Gbetagamma did not result from effects on proteasome function. Thus, PLIC-1 inhibits Gi signaling by direct association with Gbetagamma; because it also interacts with CD47, a modulator of integrin function, it likely has a role integrating adhesion and signaling components of cell migration.
Mesh Terms:
Animals, Antigens, CD3, Carrier Proteins, Cell Cycle Proteins, Cell Movement, Chemokine CXCL12, Chemokines, CXC, Cysteine Endopeptidases, Endocytosis, Enzyme Activation, Epithelial Cells, GTP-Binding Protein alpha Subunits, Gi-Go, Heterotrimeric GTP-Binding Proteins, Humans, Isoenzymes, Jurkat Cells, Multienzyme Complexes, Phospholipase C beta, Phylogeny, Proteasome Endopeptidase Complex, Protein Subunits, Receptors, CXCR4, Signal Transduction, Type C Phospholipases, Ubiquitins
J. Cell Biol.
Date: Dec. 08, 2003
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