A Unique Sequence of the Laminin α3 G Domain Binds to Heparin and Promotes Cell Adhesion through Syndecan-2 and -4*
A Unique Sequence of the Laminin α3 G Domain Binds to Heparin and Promotes Cell Adhesion through Syndecan-2 and -4*
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层粘连蛋白 α3 G 结构域的独特序列与肝素结合并通过 Syndecan-2 和 -4* 促进细胞粘附
DOI：
10.1074/jbc.m101420200
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发表时间：
2001
期刊：
影响因子：
--
通讯作者：
H. Shinkai
中科院分区：
文献类型：
--
作者：
A. Utani;M. Nomizu;H. Matsuura;Kozue Kato;Takashi Kobayashi;Ushio Takeda;S. Aota;P. K. Nielsen;H. Shinkai
层粘连蛋白-5由α3、β3和γ2链组成，位于皮肤基底膜中，支持表皮-真皮连接的结构稳定性并调节各种细胞功能。层粘连蛋白的α链具有多种生物活性。在这项研究中，我们确定了一个序列的α3链C-末端球状结构域（LG 1-LG 5模块）所需的肝素结合和细胞粘附使用重组蛋白和合成肽。我们发现LG 3和LG 4模块具有肝素结合活性，并且LG 4具有细胞粘附活性。用合成肽进行的研究将LG 4内的A3 G75 aR序列（NSFMALYLSKGR，残基1412-1423）描述为肝素和细胞结合的主要位点。LG 4和A3 G75 aR中的取代突变鉴定了A3 G75 aR序列的Lys和Arg对这些活性至关重要。细胞粘附LG 4和A3 G75 aR的抑制肝素酶I治疗的细胞，表明细胞结合A3 G75 aR网站介导的细胞表面硫酸乙酰肝素蛋白多糖。我们通过亲和层析显示，来自成纤维细胞的多配体蛋白聚糖-2与LG 4结合。固相分析证实syndecan-2与A3 G75 aR肽序列相互作用。用多配体蛋白聚糖-2和-4但不是磷脂酰肌醇蛋白聚糖-1的表达载体稳定转染的293 T细胞特异性粘附于LG 4和A3 G75 aR。这些结果表明，层粘连蛋白α3 LG 4模块内的A3 G75 aR序列负责细胞粘附，并表明多配体蛋白聚糖-2和-4介导该活性。
Laminin-5, consisting of the α3, β3, and γ2 chains, is localized in the skin basement membrane and supports the structural stability of the epidermo-dermal linkage and regulates various cellular functions. The α chains of laminins have been shown to have various biological activities. In this study, we identified a sequence of the α3 chain C-terminal globular domain (LG1-LG5 modules) required for both heparin binding and cell adhesion using recombinant proteins and synthetic peptides. We found that the LG3 and LG4 modules have activity for heparin binding and that LG4 has activity for cell adhesion. Studies with synthetic peptides delineated the A3G75aR sequence (NSFMALYLSKGR, residues 1412–1423) within LG4 as a major site for both heparin and cell binding. Substitution mutations in LG4 and A3G75aR identified the Lys and Arg of the A3G75aR sequence as critical for these activities. Cell adhesion to LG4 and A3G75aR was inhibited by heparitinase I treatment of cells, suggesting that cell binding to the A3G75aR site was mediated by cell surface heparan sulfate proteoglycans. We showed by affinity chromatography that syndecan-2 from fibroblasts bound to LG4. Solid-phase assays confirmed that syndecan-2 interacted with the A3G75aR peptide sequence. Stably transfected 293T cells with expression vectors for syndecan-2 and -4, but not glypican-1, specifically adhered to LG4 and A3G75aR. These results indicate that the A3G75aR sequence within the laminin α3 LG4 module is responsible for cell adhesion and suggest that syndecan-2 and -4 mediate this activity.
影响因子：
4
作者：
Lawrence E. Goldfinger;S. Hopkinson;Gregory W Dehart;Sherry S. Collawn;J. Couchman;Jonathan C. R. Jones
通讯作者：
Lawrence E. Goldfinger;S. Hopkinson;Gregory W Dehart;Sherry S. Collawn;J. Couchman;Jonathan C. R. Jones
锚定丝蛋白加里宁是作为高分子量前体合成和分泌的。
DOI：
--
发表时间：
1992
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Marinkovich,MP;Lunstrum,GP;Burgeson,RE
通讯作者：
Burgeson,RE
硫酸乙酰肝素、多配体聚糖和细胞行为的协调调节。
影响因子：
7.5
作者：
Rapraeger,AC
通讯作者：
Rapraeger,AC