Syndecan-1 signals independently of beta1 integrins during Raji cell spreading.
Syndecan-1 signals independently of beta1 integrins during Raji cell spreading.
复制标题
Raji 细胞扩散过程中 Syndecan-1 信号独立于 β1 整合素。
DOI：
10.1006/excr.2000.4981
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发表时间：
2000
影响因子：
3.7
通讯作者：
Rapraeger,AC
中科院分区：
文献类型：
--
作者：
Lebakken,CS;McQuade,KJ;Rapraeger,AC
表达Syndecan-1的Raji淋巴样细胞（Raji-S1细胞）在附着于含有硫酸乙酰肝素结合结构域的基质配体时结合并迅速扩散。然而，这些配体也含有整合素的结合位点，这是众所周知的信号，提出了蛋白聚糖核心蛋白是否参与产生的信号传播的问题。为了解决这个问题，在已知存在于Raji细胞上的β1整联蛋白或多配体蛋白聚糖-1核心蛋白的特异性配体上检查Raji-S1细胞的扩散。细胞在侵袭素（一种激活β1整联蛋白的配体）、纤连蛋白的IIICS片段（α4β1整联蛋白的特异性配体）或mAb 281.2（一种对syndecan-1核心蛋白具有特异性的抗体）上粘附和扩散。由粘附到多配体特异性抗体产生的信号传导表现为不依赖于整联蛋白，因为（i）在抗体上铺展的细胞的形态不同于单独由整联蛋白引发的铺展;（ii）在多配体或整联蛋白配体上铺展受到激酶抑制剂酪氨酸磷酸化抑制剂25、染料木黄酮和星形孢菌素的不同影响;和（iii）通过用β1抑制性抗体mAb 13阻断β1整联蛋白活化，不破坏在多配体特异性抗体上的铺展。这些数据表明，多配体蛋白聚糖-1的连接启动细胞内信号传导，并表明这种信号传导发生时，表达多配体蛋白聚糖-1的细胞粘附到含有硫酸乙酰肝素结合结构域的基质配体。
Syndecan-1-expressing Raji lymphoid cells (Raji-S1 cells) bind and spread rapidly when attaching to matrix ligands that contain heparan sulfate-binding domains. However, these ligands also contain binding sites for integrins, which are widely known to signal, raising the question of whether the proteoglycan core protein participates in generation of the signal for spreading. To address this question, the spreading of the Raji-S1 cells is examined on ligands specific for either β1 integrins, known to be present on the Raji cells, or the syndecan-1 core protein. The cells adhere and spread on invasin, a ligand that activates β1 integrins, the IIICS fragment of fibronectin, which is a specific ligand for the α4β1 integrin, or mAb281.2, an antibody specific for the syndecan-1 core protein. The signaling resulting from adhesion to the syndecan-specific antibody appears integrin independent as (i) the morphology of the cells spreading on the antibody is distinct from spreading initiated by the integrins alone; (ii) spreading on the syndecan or integrin ligands is affected differently by the kinase inhibitors tyrphostin 25, genistein, and staurosporine; and (iii) spreading on the syndecan-specific antibody is not disrupted by blocking β1 integrin activation with mAb13, a β1 inhibitory antibody. These data demonstrate that ligation of syndecan-1 initiates intracellular signaling and suggest that this signaling occurs when cells expressing syndecan-1 adhere to matrix ligands containing heparan sulfate-binding domains.