Cytoplasmic interactions of syndecan-4 orchestrate adhesion receptor and growth factor receptor signalling

Biochem J. 2002 Nov 15;368(Pt 1):1-15. doi: 10.1042/BJ20021228.

Abstract

Syndecan-4 is a ubiquitous transmembrane proteoglycan that localizes to the focal adhesions of adherent cells and binds to a range of extracellular ligands, including growth factors and extracellular-matrix proteins. Engagement of syndecan-4 is essential for adhesion formation in cells adhering via certain integrins, and for cell proliferation and migration in response to growth factors. The cytoplasmic domain of syndecan-4 interacts with a number of signalling and structural proteins, and both extracellular and cytoplasmic domains are necessary for regulated activation of associated transmembrane receptors. PDZ domain-containing scaffold proteins (syntenin and CASK) bind to the C-terminus of the syndecan-4 cytoplasmic domain and co-ordinate clustering of receptors and connection to the actin cytoskeleton. Syndecan-4 also binds and activates protein kinase Calpha in the presence of phosphatidylinositol 4,5-bisphosphate, and regulates signalling by Rho-family GTPases and focal adhesion kinase. This review discusses the cytoplasmic interactions of syndecan-4 and how they affect cell behaviour as a consequence of the interaction with extracellular ligands. These conclusions also offer an insight into the role of syndecan-4 in vivo, and are consistent with phenotypes generated as a consequence of abnormal syndecan-4 expression in pathologies and gene disruption studies.

Publication types

  • Review

MeSH terms

  • Actins / metabolism
  • Animals
  • Cell Adhesion / physiology*
  • Cells, Cultured
  • Cytoplasm / metabolism
  • Dimerization
  • Extracellular Matrix / metabolism
  • Heparitin Sulfate / chemistry
  • Heparitin Sulfate / metabolism
  • Humans
  • Membrane Glycoproteins / chemistry
  • Membrane Glycoproteins / metabolism*
  • Membrane Proteins / metabolism*
  • Phosphorylation
  • Platelet Glycoprotein GPIb-IX Complex
  • Proteoglycans / chemistry
  • Proteoglycans / metabolism*
  • Receptors, Growth Factor / metabolism*
  • Signal Transduction / physiology
  • Syndecan-4
  • Wound Healing / physiology
  • rho GTP-Binding Proteins / metabolism

Substances

  • Actins
  • Membrane Glycoproteins
  • Membrane Proteins
  • Platelet Glycoprotein GPIb-IX Complex
  • Proteoglycans
  • Receptors, Growth Factor
  • SDC4 protein, human
  • Syndecan-4
  • adhesion receptor
  • Heparitin Sulfate
  • rho GTP-Binding Proteins