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. 2004 Mar 15;378(Pt 3):1007–1014. doi: 10.1042/BJ20031734

Syndecan-4 regulates localization, activity and stability of protein kinase C-alpha.

Eunyoung Keum 1, Yeonhee Kim 1, Jungyean Kim 1, Soojin Kwon 1, Yangmi Lim 1, Innoc Han 1, Eok-Soo Oh 1
PMCID: PMC1224027  PMID: 14670076

Abstract

During cell-matrix adhesion, syndecan-4 transmembrane heparan sulphate proteoglycan plays a critical role in the formation of focal adhesions and stress fibres. We have shown previously that the syndecan-4 cytoplasmic domain directly binds to and activates PKC-alpha (protein kinase C-alpha) in vitro [Oh, Woods and Couchman (1997) J. Biol. Chem. 272, 8133-8136]. However, whether syndecan-4 has the same activity in vivo needs to be addressed. Using mammalian two-hybrid assays, we showed that syndecan-4 interacted with PKC-alpha in vivo and that this interaction was mediated through syndecan-4 cytoplasmic domain. Furthermore, the activation of PKC increased the extent of interaction between syndecan-4 and PKC-alpha. Overexpression of syndecan-4, but not a mutant lacking its cytoplasmic domain, specifically increased the level of endogenous PKC-alpha and enhanced the translocation of PKC-alpha into both detergent-insoluble and membrane fractions. In addition, rat embryo fibroblasts overexpressing syndecan-4 exhibited a slowed down-regulation of PKC-alpha in response either to a prolonged treatment with PMA or to maintaining cells in suspension culture. PKC-alpha immunocomplex kinase assays also showed that syndecan-4 overexpression increased the activity of membrane PKC-alpha. Taken together, these results suggest that syndecan-4 interacts with PKC-alpha in vivo and regulates its localization, activity and stability.

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Selected References

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