The ubiquitously expressed Csk adaptor protein Cbp is dispensable for embryogenesis and T-cell development and function
The ubiquitously expressed Csk adaptor protein Cbp is dispensable for embryogenesis and T-cell development and function
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DOI：
10.1128/mcb.25.23.10533-10542.2005
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发表时间：
2005-12-01
影响因子：
5.3
通讯作者：
Tarakhovsky, A
中科院分区：
文献类型：
--
作者：
Dobenecker, MW;Schmedt, C;Tarakhovsky, A
Src家族激酶（SFK）活性的调节对于功能性免疫系统和胚胎发生是必不可少的。SFKs的活性受到细胞膜上羧基末端Src激酶（Csk）的抑制。因此，招募胞浆Csk的膜相关的SFKs是至关重要的，其调节功能。以前的研究利用体外和转基因模型表明，Csk结合蛋白（CBP），也称为磷蛋白与鞘糖脂微结构域（PAG），是Csk的膜适配器。然而，缺乏支持这一观点的功能丧失遗传学证据。在此，我们证明了cbp基因在小鼠中的靶向破坏对体内胚胎发生、胸腺发育或T细胞功能没有影响。此外，Cbp缺乏不会损害Csk向“脂筏”专门膜室的募集。我们的研究结果表明，Cbp的招聘Csk的膜和另一个Csk适配器，尚未被发现，补偿Cbp的损失。
Regulation of Src family kinase (SFK) activity is indispensable for a functional immune system and embryogenesis. The activity of SFKs is inhibited by the presence of the carboxy-terminal Src kinase (Csk) at the cell membrane. Thus, recruitment of cytosolic Csk to the membrane-associated SFKs is crucial for its regulatory function. Previous studies utilizing in vitro and transgenic models suggested that the Csk-binding protein (Cbp), also known as phosphoprotein associated with glycosphingolipid microdomains (PAG), is the membrane adaptor for Csk. However, loss-of-function genetic evidence to support this notion was lacking. Herein, we demonstrate that the targeted disruption of the cbp gene in mice has no effect on embryogenesis, thymic development, or T-cell functions in vivo. Moreover, recruitment of Csk to the specialized membrane compartment of ''lipid rafts" is not impaired by Cbp deficiency. Our results indicate that Cbp is dispensable for the recruitment of Csk to the membrane and that another Csk adaptor, yet to be discovered, compensates for the loss of Cbp.