Signaling through CD44 Is Mediated by Tyrosine Kinases
Signaling through CD44 Is Mediated by Tyrosine Kinases
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DOI：
10.1074/jbc.271.5.2863
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发表时间：
1996-02
期刊：
影响因子：
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通讯作者：
T. Taher;L. Smit;A. Griffioen;E. Schilder-Tol;J. Borst;S. Pals
中科院分区：
文献类型：
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作者：
T. Taher;L. Smit;A. Griffioen;E. Schilder-Tol;J. Borst;S. Pals
来自大量研究的证据表明，CD 44参与许多重要的生物学过程，包括淋巴细胞活化和归巢、造血以及肿瘤进展和转移。对CD 44在这些过程中的作用的正确理解受到严重阻碍，因为缺乏对CD 44与细胞内信号转导途径通信模式的了解。在这份报告中，我们已经解决了这方面的CD 44功能的研究CD 44信号在T淋巴细胞。我们表明，通过单克隆抗体（mAb）连接CD 44将信号转导至T细胞，从而导致ZAP-70和其他细胞内蛋白的酪氨酸磷酸化。在体外激酶测定表明，交联的CD 44诱导增加的内在活性的p56 lck。此外，免疫沉淀显示，CD 44与p56 lck物理相关。我们的研究结果表明，酪氨酸激酶，特别是p56 lck，在CD 44介导的信号转导中发挥着重要作用。
Evidence from a large body of studies indicates that CD44 is involved in a number of important biological processes, including lymphocyte activation and homing, hematopoiesis, and tumor progression and metastasis. A proper understanding of the role of CD44 in these processes has been severely hampered by a lack of insight into the mode in which CD44 communicates with intracellular signal transduction pathways. In this report, we have addressed this aspect of CD44 functioning by studying CD44 signaling in T lymphocytes. We show that ligation of CD44 by monoclonal antibodies (mAbs) transduces signals to T cells which lead to tyrosine phosphorylation of ZAP-70 and other intracellular proteins. In vitro kinase assays demonstrate that cross-linking of CD44 induces an increase in the intrinsic activity of p56lck. Furthermore, immunoprecipitations show that CD44 is physically associated with p56lck. Our findings suggest that tyrosine kinases, particularly p56lck, play a central role in CD44 mediated signaling.