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J Biol Chem. 2016 Jan 8;291(2):872-81. doi: 10.1074/jbc.M115.685040. Epub 2015 Nov 24.

The Conserved Phenylalanine in the Transmembrane Domain Enhances Heteromeric Interactions of Syndecans.

Author information

1
From the Department of Life Sciences, Research Center for Cellular Homeostasis, Ewha Womans University, Seoul 120-750, Korea and.
2
the Seoul Center, Korea Basic Science Institute, Seoul 136-075, Korea.
3
From the Department of Life Sciences, Research Center for Cellular Homeostasis, Ewha Womans University, Seoul 120-750, Korea and OhES@ewha.ac.kr.

Abstract

The transmembrane domain (TMD) of the syndecans, a family of transmembrane heparin sulfate proteoglycans, is involved in forming homo- and heterodimers and oligomers that transmit signaling events. Recently, we reported that the unique phenylalanine in TMD positively regulates intramolecular interactions of syndecan-2. Besides the unique phenylalanine, syndecan-2 contains a conserved phenylalanine (SDC2-Phe-169) that is present in all syndecan TMDs, but its function has not been determined. We therefore investigated the structural role of SDC2-Phe-169 in syndecan TMDs. Replacement of SDC2-Phe-169 by tyrosine (S2F169Y) did not affect SDS-resistant homodimer formation but significantly reduced SDS-resistant heterodimer formation between syndecan-2 and -4, suggesting that SDC2-Phe-169 is involved in the heterodimerization/oligomerization of syndecans. Similarly, in an in vitro binding assay, a syndecan-2 mutant (S2(F169Y)) showed a significantly reduced interaction with syndecan-4. FRET assays showed that heteromolecular interactions between syndecan-2 and -4 were reduced in HEK293T cells transfected with S2(F169Y) compared with syndecan-2. Moreover, S2(F169Y) reduced downstream reactions mediated by the heterodimerization of syndecan-2 and -4, including Rac activity, cell migration, membrane localization of PKCα, and focal adhesion formation. The conserved phenylalanine in syndecan-1 and -3 also showed heterodimeric interaction with syndecan-2 and -4. Taken together, these findings suggest that the conserved phenylalanine in the TMD of syndecans is crucial in regulating heteromeric interactions of syndecans.

KEYWORDS:

heterodimerization; oligomerization; receptor regulation; signal transduction; syndecan; transmembrane domain

PMID:
26601939
PMCID:
PMC4705405
DOI:
10.1074/jbc.M115.685040
[Indexed for MEDLINE]
Free PMC Article

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