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.
N'Diaye
Elsa-Noah
EN
Program in Host-Pathogen Interactions, University of California, San Francisco, Campus Box 2140, 600 16th St., San Francisco, CA 94143-2140, USA.
Brown
Eric J
EJ
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D000071183:Autophagy-Related Proteins; D017252:CD3 Complex / Q000378:metabolism; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D002465:Cell Movement / Q000502:physiology; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000378:metabolism; D003546:Cysteine Endopeptidases / Q000378:metabolism; D004705:Endocytosis; D004789:Enzyme Activation; D004847:Epithelial Cells / Q000378:metabolism; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000378:metabolism; D020962:Heterotrimeric GTP-Binding Proteins / Q000378:metabolism*; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D019169:Jurkat Cells; D009097:Multienzyme Complexes / Q000378:metabolism; D054799:Phospholipase C beta; D010802:Phylogeny; D046988:Proteasome Endopeptidase Complex; D021122:Protein Subunits / Q000378:metabolism*; D019718:Receptors, CXCR4 / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D010738:Type C Phospholipases / Q000378:metabolism; D014452:Ubiquitins / Q000145:classification / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D000071183:Autophagy-Related Proteins; D017252:CD3 Complex; C515255:CXCL12 protein, human; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D007527:Isoenzymes; D009097:Multienzyme Complexes; D021122:Protein Subunits; D019718:Receptors, CXCR4; C107792:UBQLN1 protein, human; C405662:UBQLN2 protein, human; D014452:Ubiquitins; D010738:Type C Phospholipases; D054799:Phospholipase C beta; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D020962:Heterotrimeric GTP-Binding Proteins