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Trans-regulation of Syndecan Functions by Hetero-oligomerization

Title
Trans-regulation of Syndecan Functions by Hetero-oligomerization
Authors
Choi, YoungsilKwon, Mi-JungLim, YangmiYun, Ji-HyeLee, WeontaeOh, Eok-Soo
Ewha Authors
오억수
SCOPUS Author ID
오억수scopus
Issue Date
2015
Journal Title
JOURNAL OF BIOLOGICAL CHEMISTRY
ISSN
0021-9258JCR Link1083-351XJCR Link
Citation
vol. 290, no. 27, pp. 16943 - 16953
Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
Syndecans, a family of transmembrane heparansulfate proteoglycans, are known to interact through their transmembrane domains to form non-covalently linked homodimers, a process essential for their individual functions. Because all syndecan transmembrane domains are highly conserved and thus might mediate interactions between different members of the syndecan family, we investigated syndecan interactions in detail. All recombinant syndecan-2 and -4 protein variants containing the transmembrane domain formed not only sodium dodecyl sulfate (SDS)-resistant homodimers but also SDS-resistant heterodimers. Biochemical and structural data revealed that recombinant syndecan-2 and -4 formed intermolecular interactions in vitro, and the GXXXG motif in transmembrane domain mediated this interaction. When exogenously expressed in rat embryonic fibroblasts, syndecan-2 interacted with syndecan-4 and vice versa. Furthermore, bimolecular fluorescence complementation-based assay demonstrated specific hetero-molecular interactions between syndecan-2 and -4, supporting hetero-oligomer formation of syndecans in vivo. Interestingly, hetero-oligomerization significantly reduced syndecan-4-mediated cellular processes such as protein kinase C alpha activation and protein kinase C alpha-mediated cell adhesion as well as syndecan-2-mediated tumorigenic activities in colon cancer cells such as migration and anchorage-independent growth. Taken together, these data provide evidence that hetero-oligomerization produces distinct syndecan functions and offer insights into the underlying signaling mechanisms of syndecans.
DOI
10.1074/jbc.M114.611798
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자연과학대학 > 생명과학전공 > Journal papers
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