The PI3K effector Arap3 interacts with the PI(3,4,5)P3 phosphatase SHIP2 in a SAM domain-dependent manner
The PI3K effector Arap3 interacts with the PI(3,4,5)P3 phosphatase SHIP2 in a SAM domain-dependent manner
复制标题
DOI：
10.1016/j.cellsig.2006.12.015
复制
发表时间：
2007-06-01
影响因子：
4.8
通讯作者：
Bos, Johannes L.
中科院分区：
文献类型：
--
作者：
Raaijmakers, Judith H.;Deneubourg, Laurence;Bos, Johannes L.
Arap 3是磷酸肌醇（PI）3激酶效应物，其充当Arf和Rho G-蛋白的GTP酶激活蛋白（GAP）。该蛋白具有多个普列克底物蛋白同源（PH）结构域，其优先结合磷脂酰肌醇-3，4，5-三磷酸（PI（3，4，5，）P-3）以在PI 3 K活化时诱导Arap 3易位至质膜。Arap 3还包含一个Ras相关（RA）结构域，与小G蛋白Rap I和一个功能未知的不育α基序（SAM）结构域相互作用。在酵母双杂交筛选Arap 3的新相互作用伴侣中，我们鉴定了PI 5 '-磷酸酶SHIP 2作为Arap 3的相互作用伴侣。Arap 3和SHIP 2之间的相互作用被观察到与内源性蛋白质，并被证明是由SAM结构域的Arap 3和SHIP 2。在体外，这两个结构域显示出异二聚体相互作用的特异性。由于之前已经显示Arap 3对PI（3，4，5，）P-3的亲和力比对PI（3，4）P-2的亲和力高，我们提出Arap（3）的SAM结构域可以起到将PI 3 K信号传导的负调节剂募集到效应复合物中的作用。(c)2007年爱思唯尔公司All rights reserved.
Arap3 is a phosphoinositide (PI) 3 kinase effector that serves as a GTPase activating protein (GAP) for both Arf and Rho G-proteins. The protein has multiple pleckstrin homology (PH) domains that bind preferentially phosphatidyl-inositol-3,4,5-trisphosphate (PI(3,4,5,)P-3) to induce translocation of Arap3 to the plasma membrane upon PI3K activation. Arap3 also contains a Ras association (RA) domain that interacts with the small G-protein Rap I and a sterile alpha motif (SAM) domain of unknown function. In a yeast two-hybrid screen for new interaction partners of Arap3, we identified the PI 5'-phosphatase SHIP2 as an interaction partner of Arap3. The interaction between Arap3 and SHIP2 was observed with endogenous proteins and shown to be mediated by the SAM domain of Arap3 and SHIP2. In vitro, these two domains show specificity for a heterodimeric interaction. Since it was shown previously that Arap3 has a higher affinity for PI(3,4,5,)P-3 than for PI(3,4)P-2, we propose that the SAM domain of Arap(3) can function to recruit a negative regulator of PI3K signaling into the effector complex. (c) 2007 Elsevier Inc. All rights reserved.