Abstract
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.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adaptor Proteins, Signal Transducing
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Animals
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Autophagy-Related Proteins
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CD3 Complex / metabolism
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Carrier Proteins*
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Cell Cycle Proteins*
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Cell Movement / physiology
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Chemokine CXCL12
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Chemokines, CXC / metabolism
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Cysteine Endopeptidases / metabolism
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Endocytosis
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Enzyme Activation
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Epithelial Cells / metabolism
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GTP-Binding Protein alpha Subunits, Gi-Go / metabolism
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Heterotrimeric GTP-Binding Proteins / metabolism*
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Humans
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Isoenzymes / metabolism
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Jurkat Cells
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Multienzyme Complexes / metabolism
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Phospholipase C beta
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Phylogeny
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Proteasome Endopeptidase Complex
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Protein Subunits / metabolism*
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Receptors, CXCR4 / metabolism
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Signal Transduction / physiology
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Type C Phospholipases / metabolism
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Ubiquitins / classification
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Ubiquitins / metabolism*
Substances
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Adaptor Proteins, Signal Transducing
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Autophagy-Related Proteins
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CD3 Complex
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CXCL12 protein, human
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Carrier Proteins
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Cell Cycle Proteins
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Chemokine CXCL12
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Chemokines, CXC
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Isoenzymes
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Multienzyme Complexes
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Protein Subunits
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Receptors, CXCR4
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UBQLN1 protein, human
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UBQLN2 protein, human
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Ubiquitins
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Type C Phospholipases
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Phospholipase C beta
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Cysteine Endopeptidases
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Proteasome Endopeptidase Complex
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GTP-Binding Protein alpha Subunits, Gi-Go
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Heterotrimeric GTP-Binding Proteins