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PubMed · 12372401

Ligand-specific control of src-suppressed C kinase substrate gene expression.

Stephen R Coats·Lil M Pabón-Peña·Joseph W Covington·Douglas E Vaughan
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Abstract

The src-suppressed C-kinase substrate, SSeCKS, is now recognized as a key regulator of cell signaling and cytoskeletal dynamics. However, few ligands that control SSeCKS expression have been identified. We report that platelet-derived growth factor-BB (PDGF-BB), lysophosphatidic acid (LPA), and eicosapentaenoic acid (EPA) potently modulate SSeCKS gene expression in cultured smooth muscle (RASM) cells relative to other bioactive ligands tested. In addition, EPA-dependent regulation of SSeCKS expression correlates with distinct changes in cell morphology and adhesion in RASM cells. Independent evidence that ligand-specific control of SSeCKS expression links to the regulation of cell adhesion and morphology was obtained using ras-transformed fibroblasts, KNRK. Sodium butyrate (NaB) upregulates SSeCKS mRNA and protein expression corresponding to increased cell-spreading and adhesion. In addition, ectopic expression of recombinant SSeCKS recapitulates attributes of NaB-induced morphogenesis in KNRK cells. The data provide novel evidence that SSeCKS functions in PDGF-BB-, LPA-, EPA-, and NaB-mediated cell signaling.

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A Kinase Anchor ProteinsAnimalsBecaplerminBlotting, WesternCell AdhesionCell Cycle ProteinsCell DifferentiationCell DivisionCell Line, TransformedCells, CulturedCloning, MolecularDose-Response Relationship, DrugEicosapentaenoic AcidFibroblastsImmunohistochemistryLigandsLysophospholipidsMicroscopy, FluorescenceMitogensMuscle, SmoothPlatelet-Derived Growth FactorProtein BindingProto-Oncogene Proteins c-sisProto-Oncogene Proteins pp60(c-src)RatsRecombinant ProteinsReverse Transcriptase Polymerase Chain ReactionSignal TransductionSodium OxybateTime FactorsUp-RegulationJournal ArticleResearch Support, U.S. Gov't, P.H.S.

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Stephen R Coats, Lil M Pabón-Peña, Joseph W Covington, Douglas E Vaughan. 2002-10-11. Ligand-specific control of src-suppressed C kinase substrate gene expression.. https://doi.org/10.1016/s0006-291x(02)02275-1

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