A WD-FYVE protein binds to the kinases Akt and PKCζ/λ
A WD-FYVE protein binds to the kinases Akt and PKCζ/λ
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DOI：
10.1042/bj20060511
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发表时间：
2006-10-01
影响因子：
4.1
通讯作者：
Moelling, Karin
中科院分区：
文献类型：
--
作者：
Fritzius, Thorsten;Burkard, Gabriela;Moelling, Karin
WD（色氨酸-天冬氨酸二肽）重复蛋白通过协调关键信号分子的相互作用，在信号转导级联中发挥核心作用。我们鉴定了一种新型螺旋桨-FYVE [在 Fab1p、YOTB、Vac1p 和 EEA1（早期内体抗原 1）中鉴定的结构域] 蛋白 ProF，它在各种细胞系和组织中表达，由七个 WD 重复序列和一个 FYVE 结构域组成。 WD 重复蛋白通过折叠成七叶螺旋桨状结构，为蛋白质-蛋白质相互作用提供了一个平台，而 FYVE 结构域则与主要存在于细胞内膜上的磷脂酰肌醇 3-磷酸结合。 ProF 蛋白与 EEA1 部分共定位于囊泡结构上，并通过其 WD 重复螺旋桨与蛋白激酶 Akt 和 PKC zeta/lambda（蛋白激酶 C zeta/lambda）结合。激素刺激后，ProF 与激酶的相互作用更加强烈。内源表达的 ProF 和两种激酶在大脑和前脂肪细胞系 3T3-L1 中相互作用，表明在分泌性囊泡过程中发挥作用。总之，我们描述了一种新的激酶结合伴侣，位于特殊细胞的囊泡结构上，它可能在信号级联的空间组织中发挥作用。
WD (tryptophan-aspartic acid dipeptide)-repeat proteins play a central role in signal transduction cascades by co-ordinating the interaction of key signalling molecules. We identified a novel propeller-FYVE [domain identified in Fab1p, YOTB, Vac1p and EEA1 (early endosome antigen 1)] protein, ProF, which is expressed in various cell lines and tissues and consists of seven WD-repeats and a FYVE domain. WD-repeat proteins offer a platform for protein-protein interactions by folding into a seven-bladed propeller-like structure, while the FYVE domain binds to phosphatidylinositol 3-phosphate present mainly on intracellular membranes. The ProF protein partially co-localizes with EEA1 on vesicular structures and binds to the protein kinases Akt and PKC zeta/lambda (protein kinase C zeta/lambda) via its WD-repeat propeller. ProF interacts more strongly with the kinases after hormonal stimulation. Endogenously expressed ProF and the two kinases interact in brain and in the preadipocyte cell line 3T3-L1, suggesting a role in secretory vesicular processes. In summary, we describe a new binding partner for kinases, located on vesicular structures in specialized cells, which may play a role for the spatial organization of signalling cascades.