WISP-1 binds to decorin and biglycan
WISP-1 binds to decorin and biglycan
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DOI：
10.1074/jbc.m108339200
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发表时间：
2001-12-14
影响因子：
4.8
通讯作者：
Pennica, D
中科院分区：
文献类型：
--
作者：
Desnoyers, L;Arnott, D;Pennica, D
wnt -1诱导分泌蛋白1 （WISP-1）是CCN（结缔组织生长因子，Cyr61， NOV）生长因子家族的一员。结构和实验证据表明，CCN家族成员的活性是由它们与硫酸糖缀合物的相互作用调节的。为了阐明WISP-1的作用机制，我们对其组织和细胞相互作用的特异性进行了表征，并鉴定了结合因子。WISP-1的结合仅限于结肠肿瘤基质和成纤维细胞表型。通过固相实验，我们发现人皮肤成纤维细胞条件培养基中含有WISP-1结合因子。不同糖胺聚糖的竞争性抑制以及糖胺聚糖裂解酶和蛋白酶的处理表明，与条件培养基的结合是由硫酸皮肤聚糖蛋白聚糖介导的。质谱分析鉴定分离的结合因子为decorin和biglycan。Decorin和biglycan直接与WISP-1相互作用，抑制其与条件介质中组分的结合。同样，通过皮肤硫酸酯、decorin和biglycan或皮肤硫酸酯特异性裂解酶处理细胞表面，可以抑制WISP-I与人皮肤成纤维细胞的相互作用。综上所述，这些结果表明decorin和biglycan是WISP-1结合因子，可以介导和调节WISP-1与成纤维细胞表面的相互作用。我们认为这种特定的相互作用在WISP-1功能的调控中起作用。
Wnt-1-induced secreted protein 1 (WISP-1) is a member of the CCN (connective tissue growth factor, Cyr61, NOV) family of growth factors. Structural and experimental evidence suggests that CCN family member activities are modulated by their interaction with sulfated glycoconjugates. To elucidate the mechanism of action for WISP-1, we characterized the specificity of its tissue and cellular interaction and identified binding factors. WISP-1 binding was restricted to the stroma of colon tumors and to cells with a fibroblastic phenotype. By using a solid phase assay, we showed that human skin fibroblast conditioned media contained WISP-1 binding factors. Competitive inhibition with different glycosaminoglycans and treatment with glycosaminoglycan lyases and proteases demonstrated that binding to the conditioned media was mediated by dermatan sulfate proteoglycans. Mass spectrometric analysis identified the isolated binding factors as decorin and biglycan. Decorin and biglycan interacted directly with WISP-1 and inhibited its binding to components in the conditioned media. Similarly, WISP-I interaction with human skin fibroblasts was inhibited by dermatan sulfate, decorin, and biglycan or by treatment of the cell surface with dermatan sulfate-specific lyases. Together these results demonstrate that decorin and biglycan are WISP-1 binding factors that can mediate and modulate its interaction with the surface of fibroblasts. We propose that this specific interaction plays a role in the regulation of WISP-1 function.