The PH domain containing protein CKIP-1 binds to IFP35 and Nmi and is involved in cytokine signaling
The PH domain containing protein CKIP-1 binds to IFP35 and Nmi and is involved in cytokine signaling
复制标题
含有 CKIP-1 蛋白的 PH 结构域与 IFP35 和 Nmi 结合，并参与细胞因子信号传导。
DOI：
10.1016/j.cellsig.2006.11.002
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发表时间：
2007-05-01
影响因子：
4.8
通讯作者：
He, Fuchu
中科院分区：
文献类型：
--
作者：
Zhang, Lingqiang;Tang, Ying;He, Fuchu
含有普列克底物蛋白同源结构域的蛋白CKIP-1涉及细胞分化、凋亡、细胞骨架的调节以及CK 2和ATM激酶向质膜的募集。这些功能需要CKIP-1的蛋白质-蛋白质相互作用。在这里，我们确定了IFN诱导的蛋白IFP 35和它的同系物Nmi作为两个新的CKIP-1相互作用的合作伙伴。IFP 35和Nmi的NID结构域是相互作用所必需的。与IFP 35和Nmi类似，CKIP-1可以被IFN-γ和IL-2显著上调，并在体内形成同源二聚体和同源三聚体。Nmi稳定IFP 35，而CKIP-1通过抑制IFP 35-Nmi相互作用使IFP 35不稳定。Nmi与CKIP-1的比例决定IFP 35的稳定性，并以新的机制控制细胞因子信号传导。重要的是，与Nmi类似，与IFP 35相反，CKIP-1抑制肿瘤细胞生长和Akt介导的细胞存活。因此，我们的研究结果提供了CKIP-1在细胞因子信号转导应答和生化机制中的新作用，其中两个先前鉴定的调节剂IFP 35和Nmi通过相互作用参与。(c)2006年爱思唯尔公司All rights reserved.
The pleckstrin homology domain-containing protein CKIP-1 is implicated in regulation of cell differentiation, apoptosis, cytoskeleton as well as recruitment of CK2 and ATM kinases to plasma membrane. Protein-protein interactions of CKIP-1 were required for these functions. Here we identify the IFN-induced protein IFP35 and its homologue Nmi as two novel CKIP-1 interacting partners. The NID domains of IFP35 and Nmi are required for the interactions. Similar to IFP35 and Nmi, CKIP-1 can be up-regulated dramatically by IFN-gamma and IL-2 and form homodimer and homotrimer in vivo. Nmi stabilizes IFP35, whereas CKIP-1 destabilizes IFP35 via inhibiting IFP35-Nmi interaction. The ratio of Nmi to CKIP-1 determines the stability of IFP35 and control cytokine signaling in a novel mechanism. Importantly, similar to Nmi and contrast to IFP35, CKIP-1 inhibits tumor cell growth and Akt-mediated cell survival. Thus, our results provide a novel role of CKIP-1 in cytokine signaling response and the biochemical mechanism, by which two previously identified modulators IFP35 and Nmi are involved via interactions. (c) 2006 Elsevier Inc. All rights reserved.