title: Sphingosine 1-phosphate stimulates fibronectin matrix assembly through a Rho-dependent signal pathway.
abstract: Fibronectin matrix assembly is a cell-dependent process mediated by cell surface binding sites for the 70-kD N-terminal portion of fibronectin. We have shown that Rho-dependent cytoskeleton reorganization induced by lysophosphatidic acid (LPA) or the microtubule-disrupting agent nocodazole increases fibronectin binding (Zhang et al, Mol Biol Cell 8:1415, 1997). Sphingosine 1-phosphate (S1P) is a bioactive sphingolipid implicated in mitogenesis and cytoskeletal remodelling. Both LPA and S1P are present in increased amounts in serum as compared with plasma as a result of platelet activation. Addition of S1P to human osteosarcoma MG63 cells or human foreskin fibroblasts increased cell-mediated binding and assembly of fibronectin. MG63 cells expressed the Edg-2 and Edg-4 G-protein-coupled receptors for bioactive lipids, whereas foreskin fibroblasts expressed Edg-2, Edg-3, and Edg-4. The stimulatory effect of S1P on the binding of fibronectin or the N-terminal 70-kD fragment of fibronectin was dynamic and due to increases in both the number and affinity of binding sites. The stimulation of 70-kD fragment binding by nanomolar S1P, like stimulation of binding by LPA or nocodazole, was blocked by inactivation of Rho with C3 exotoxin but not by pertussis toxin-mediated inactivation of Gi. These results indicate a common signal pathway leading to control of cellular fibronectin matrix assembly by bioactive lipids generated during blood coagulation.
authors.affiliation: Departments of Medicine and Biomolecular Chemistry, University of Wisconsin-Madison, Madison, WI, USA.
authors.forename: Q
authors.initials: Q
authors.lastname: Zhang
authors.forename: O
authors.initials: O
authors.lastname: Peyruchaud
authors.forename: K J
authors.initials: KJ
authors.lastname: French
authors.forename: M K
authors.initials: MK
authors.lastname: Magnusson
authors.forename: D F
authors.initials: DF
authors.lastname: Mosher
mesh_terms: D001665:Binding Sites; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D005109:Extracellular Matrix / Q000187:drug effects / Q000502:physiology*; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology; D005353:Fibronectins / Q000187:drug effects / Q000502:physiology*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006801:Humans; D008245:Lysophospholipase / Q000494:pharmacology; D008246:Lysophospholipids; D008297:Male; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics; D012516:Osteosarcoma; D017239:Paclitaxel / Q000494:pharmacology; D010446:Peptide Fragments / Q000378:metabolism; D037342:Pertussis Toxin; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D049368:Receptors, Lysophosphatidic Acid; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D012867:Skin / Q000166:cytology; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D014407:Tumor Cells, Cultured; D010566:Virulence Factors, Bordetella / Q000494:pharmacology; D016335:Zinc Fingers
chemical_list: D005353:Fibronectins; D008246:Lysophospholipids; D009687:Nuclear Proteins; D010446:Peptide Fragments; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D049368:Receptors, Lysophosphatidic Acid; D014157:Transcription Factors; D010566:Virulence Factors, Bordetella; C060506:sphingosine 1-phosphate; D037342:Pertussis Toxin; D008245:Lysophospholipase; D019204:GTP-Binding Proteins; D013110:Sphingosine; D017239:Paclitaxel