Indispensable roles of mammalian Cbl family proteins as negative regulators of protein tyrosine kinase signaling: Insights from in vivo models.
Indispensable roles of mammalian Cbl family proteins as negative regulators of protein tyrosine kinase signaling: Insights from in vivo models.
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DOI：
10.4161/cib.4.2.14716
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发表时间：
2011-03-01
影响因子：
--
通讯作者：
Band, Hamid
中科院分区：
文献类型：
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作者：
Naramura, Mayumi;Band, Vimla;Band, Hamid
所有高等真核生物都利用蛋白酪氨酸激酶(PTK)作为分子开关来控制各种细胞信号。值得注意的是，许多PTK已被鉴定为原癌基因，其异常表达、突变或病原体的选择性可导致人类恶性肿瘤。因此，很明显，为了维持生物体的动态平衡，必须精确地调节PTK的功能。过去15年的研究表明，Cbl家族蛋白可以作为PTK信号的负调节因子，生化和细胞生物学研究揭示了这种调节的机制基础。然而，直到最近，该领域才开始认识到这种新的调节装置在塑造组织环境中和人类疾病中PTK介导的信号方面的真正意义。在这里，我们讨论小鼠模型的最新进展，这些模型开始深入了解Cbl蛋白在生理途径中的关键作用，并对理解Cbl蛋白的异常如何促进肿瘤发生具有重要意义。
All higher eukaryotes utilize protein tyrosine kinases (PTKs) as molecular switches to control a variety of cellular signals. Notably, many PTKs have been identified as proto-oncogenes whose aberrant expression, mutations or co-option by pathogens can lead to human malignancies. Thus, it is obvious that PTK functions must be precisely regulated in order to maintain homeostasis of an organism. Investigations over the past fifteen years have revealed that members of the Cbl family proteins can serve as negative regulators of PTK signaling, and biochemical and cell biological studies have unraveled the mechanistic basis of this regulation. Yet, it is only recently that the field has begun to appreciate the real significance of this novel regulatory apparatus in shaping PTK-mediated signaling in organismic contexts and in human diseases. Here, we discuss recent progress in murine models that are beginning to provide insights into the critical roles of Cbl proteins in physiological pathways, with important implications in understanding how aberrations of Cbl proteins contribute to oncogenesis.