Ligand-specific control of src-suppressed C kinase substrate gene expression.
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.
Coats
Stephen R
SR
Department of Medicine, Vanderbilt University Medical Center and Nashville VAMC, Nashville, TN 37212-6300, USA. scoats@u.washington.edu
Pabón-Peña
Lil M
LM
Covington
Joseph W
JW
Vaughan
Douglas E
DE
D054758:A Kinase Anchor Proteins; D000818:Animals; D000077214:Becaplermin; D015153:Blotting, Western; D002448:Cell Adhesion; D018797:Cell Cycle Proteins; D002454:Cell Differentiation; D002455:Cell Division; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D003001:Cloning, Molecular; D004305:Dose-Response Relationship, Drug; D015118:Eicosapentaenoic Acid / Q000494:pharmacology; D005347:Fibroblasts / Q000378:metabolism; D007150:Immunohistochemistry; D008024:Ligands; D008246:Lysophospholipids / Q000494:pharmacology; D008856:Microscopy, Fluorescence; D008934:Mitogens / Q000737:chemistry* / Q000378:metabolism*; D009130:Muscle, Smooth / Q000166:cytology; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D011485:Protein Binding; D020574:Proto-Oncogene Proteins c-sis; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000378:metabolism; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D012978:Sodium Oxybate / Q000494:pharmacology; D013997:Time Factors; D015854:Up-Regulation
D054758:A Kinase Anchor Proteins; C102361:Akap12 protein, rat; D018797:Cell Cycle Proteins; D008024:Ligands; D008246:Lysophospholipids; D008934:Mitogens; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D011994:Recombinant Proteins; D000077214:Becaplermin; D012978:Sodium Oxybate; D015118:Eicosapentaenoic Acid; D016392:Proto-Oncogene Proteins pp60(c-src)