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Regulation of inositol phospholipid binding and signaling through syndecan-4

Title
Regulation of inositol phospholipid binding and signaling through syndecan-4
Authors
Couchman J.R.Vogt S.Lim S.-T.Lim Y.Oh E.-S.Prestwich G.D.Theibert A.Lee W.Woods A.
Ewha Authors
오억수
SCOPUS Author ID
오억수scopus
Issue Date
2002
Journal Title
Journal of Biological Chemistry
ISSN
0021-9258JCR Link
Citation
vol. 277, no. 51, pp. 49296 - 49303
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
Syndecan-4 is a transmembrane heparan sulfate proteoglycan that can regulate cell-matrix interactions and is enriched in focal adhesions. Its cytoplasmic domain contains a central region unlike that of any other vertebrate or invertebrate syndecan core protein with a cationic motif that binds inositol phospholipids. In turn, lipid binding stabilizes the syndecan in oligomeric form, with subsequent binding and activation of protein kinase C. The specificity of phospholipid binding and its potential regulation are investigated here. Highest affinity of the syndecan-4 cytoplasmic domain was seen with phosphatidylinositol 4,5-bisphosphate (PtdIns-(4,5P) 2) and phosphatidylinositol 4-phosphate, and both promoted syndecan-4 oligomerization. Affinity was much reduced for 3-phosphorylated inositides while no binding of diacylglycerol was detected. Syndecan-2 cytoplasmic domain had negligible affinity for any lipid examined. Inositol hexakisphosphate, but not inositol tetrakisphosphate, also had high affinity for the syndecan-4 cytoplasmic domain and could compete effectively with PtdIns(4,5)P 2. Since inositol hexaphosphate binding to syndecan-4 does not promote oligomer formation, it is a potential down-regulator of syndecan-4 signaling. Similarly, phosphorylation of serine 183 in syndecan-4 cytoplasmic domain reduced PtdIns(4,5)P 2 binding affinity by over 100-fold, although interaction could still be detected by nuclear magnetic resonance spectroscopy. Only protein kinaseCα was up-regulated in activity by the combination of syndecan-4 and PtdIns(4,5)P 2, with all other isoforms tested showing minimal response. This is consistent with the codistribution of syndecan-4 with the α isoform of protein kinase C in focal adhesions.
DOI
10.1074/jbc.M209679200
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자연과학대학 > 생명과학전공 > Journal papers
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