Syndecan-4 binding to the high affinity heparin-binding domain of fibronectin drives focal adhesion formation in fibroblasts.
Cell adhesion to extracellular matrix involves signaling mechanisms which control attachment, spreading and the formation of focal adhesions and stress fibers. Fibronectin can provide sufficient signals for all three processes, even when protein synthesis is prevented by cycloheximide. Primary fibroblasts attach and spread following integrin ligation, but do not form focal adhesions unless treated with a heparin-binding fragment of fibronectin (HepII), a peptide from this domain, or phorbol esters to activate protein kinase C. Syndecan-4 heparan sulfate proteoglycan is a transmembrane component present together with integrins in focal adhesions. Syndecan-4 binds and activates protein kinase Calpha, whose activity is needed for focal adhesion formation. We now report that the glycosaminoglycan chains of syndecan-4 bind recombinant HepII and it is incorporated into forming focal adhesions.
Woods
A
A
Department of Cell Biology, University of Alabama at Birmingham, Birmingham, Alabama, 35294-0019, USA. awoods@cellbio.bhs.uab.edu
Longley
R L
RL
Tumova
S
S
Couchman
J R
JR
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites / Q000187:drug effects; D001667:Binding, Competitive; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005353:Fibronectins / Q000737:chemistry / Q000378:metabolism*; D006493:Heparin / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000187:drug effects / Q000378:metabolism*; D009842:Oligopeptides / Q000138:chemical synthesis / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects; D011509:Proteoglycans / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D053671:Syndecan-4; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D005353:Fibronectins; D008562:Membrane Glycoproteins; D009842:Oligopeptides; D011509:Proteoglycans; C508307:Sdc4 protein, rat; D053671:Syndecan-4; D006493:Heparin; D013755:Tetradecanoylphorbol Acetate