Syndecan-4-mediated signalling.
The paradigm of cell surface proteoglycan function has been centered on the role of the ectoplasmic heparan sulfate (HS) chains as acceptors of a wide array of ligands, including extracellular matrix (ECM) proteins and soluble growth factors. Within this picture, the core proteins were assigned only a passive role of carrying the glycosaminoglycan (GAG) chains without direct participation in mediating outside-in signals generated by the binding of the above ligands. It appears now, however, that, side by side with the integrins and the tyrosine kinase receptors, the core proteins of the syndecan family of transmembrane proteoglycans are involved in signaling. The highly conserved tails of all the four members of the syndecan family contain a carboxy-terminal PDZ (Postsynaptic density 95, Disk large, Zona occludens-1)-binding motif, capable of forming multimolecular complexes through the binding of PDZ adaptor proteins. The cytoplasmic tail of the ubiquitously expressed syndecan-4 is distinct from the other syndecans in its capacity to bind phosphatidylinositol 4,5-bisphosphate (PIP2) and to activate protein kinase C (PKC) alpha. These properties may confer on syndecan-4 specific and unique signaling functions.
Simons
M
M
Angiogenesis Research Center, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA. michael.simons@dartmouth.edu
Horowitz
A
A
D000595:Amino Acid Sequence; D000818:Animals; D005346:Fibroblast Growth Factors / Q000502:physiology; D007527:Isoenzymes / Q000378:metabolism; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000502:physiology*; D008954:Models, Biological; D008969:Molecular Sequence Data; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism; D051571:Protein Kinase C-alpha; D017434:Protein Structure, Tertiary; D011509:Proteoglycans / Q000737:chemistry / Q000502:physiology*; D015398:Signal Transduction; D053671:Syndecan-4
D007527:Isoenzymes; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins; D019269:Phosphatidylinositol 4,5-Diphosphate; D011509:Proteoglycans; D053671:Syndecan-4; D005346:Fibroblast Growth Factors; D011493:Protein Kinase C; D051571:Protein Kinase C-alpha