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 Cα 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.
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Review Article|
November 15 2002
Cytoplasmic interactions of syndecan-4 orchestrate adhesion receptor and growth factor receptor signalling Available to Purchase
Mark D. BASS;
Mark D. BASS
Wellcome Trust Centre for Cell-Matrix Research, School of Biological Sciences, University of Manchester, Manchester M13 9PT, U.K.
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Martin J. HUMPHRIES
Martin J. HUMPHRIES
1
Wellcome Trust Centre for Cell-Matrix Research, School of Biological Sciences, University of Manchester, Manchester M13 9PT, U.K.
1To whom correspondence should be addressed (e-mail [email protected]).
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Publisher: Portland Press Ltd
Accepted Manuscript online:
September 20 2002
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London ©2002
2002
Biochem J (2002) 368 (1): 1–15.
Article history
Accepted Manuscript online:
September 20 2002
Citation
Mark D. BASS, Martin J. HUMPHRIES; Cytoplasmic interactions of syndecan-4 orchestrate adhesion receptor and growth factor receptor signalling. Biochem J 15 November 2002; 368 (1): 1–15. doi: https://doi.org/10.1042/bj20021228
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