Sorting nexin 6, a novel SNX, interacts with the transforming growth factor-β family of receptor serine-threonine kinases
Sorting nexin 6, a novel SNX, interacts with the transforming growth factor-β family of receptor serine-threonine kinases
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DOI：
10.1074/jbc.m100606200
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发表时间：
2001-06-01
影响因子：
4.8
通讯作者：
Lechleider, RJ
中科院分区：
文献类型：
--
作者：
Parks, WT;Frank, DB;Lechleider, RJ
分类连接蛋白（SNX）包括一个与几种酵母蛋白同源的蛋白家族，包括vp5p和Mvp1p，它们是将蛋白质分类到酵母液泡所必需的。人类SNX1, 2和-4被认为在受体运输中发挥作用，并已被证明与几种酪氨酸受体激酶结合，包括表皮生长因子，血小板衍生生长因子和胰岛素的受体，以及瘦素受体（一种糖蛋白130相关受体）的长形式。我们现在描述了这个家族的一个新成员，SNX6，它与转化生长因子-p受体丝氨酸-苏氨酸激酶家族的成员相互作用。这些受体分为两类：结合配体的II型受体和随后被招募来转导信号的I型受体。在II型受体中，SNX6被发现与ActRIIB有强烈的相互作用，而与野生型和激酶缺陷型T β RII突变体的相互作用则较为温和。在I型受体中，发现SNX6仅与失活的T β RI相互作用。snx1 -4也与转化生长因子-p受体家族相互作用，表现出不同的受体偏好。相反，SNX6在与受体酪氨酸激酶的相互作用中表现得与其他SNX蛋白相似。SNX1、-2、-4和-6之间也存在强的异质相互作用，表明在体内形成了低聚物复合物。这些发现是SNX分子家族与受体丝氨酸-苏氨酸激酶相关的第一个证据。
Sorting nexins (SNX) comprise a family of proteins with homology to several yeast proteins, including Vps5p and Mvp1p, that are required for the sorting of proteins to the yeast vacuole. Human SNX1, -2, and -4 have been proposed to play a role in receptor trafficking and have been shown to bind to several receptor tyrosine kinases, including receptors for epidermal growth factor, platelet-derived growth factor, and insulin as well as the long form of the leptin receptor, a glycoprotein 130-associated receptor. We now describe a novel member of this family, SNX6, which interacts with mem bers of the transforming growth factor-p family of receptor serine-threonine kinases. These receptors belong to two classes: type II receptors that bind ligand, and type I receptors that are subsequently recruited to transduce the signal. Of the type II receptors, SNX6 was found to interact strongly with ActRIIB and more moderately with wild type and kinase-defective mutants of T beta RII. Of the type I receptors, SNX6 was found to interact only with inactivated T beta RI. SNXs 1-4 also interacted with the transforming growth factor-p receptor family, showing different receptor preferences. Conversely, SNX6 behaved similarly to the other SNX proteins in its interactions with receptor tyrosine kinases. Strong heteromeric interactions were also seen among SNX1, -2, -4, and -6, suggesting the formation in vivo of oligomeric complexes. These findings are the first evidence for the association of the SNX family of molecules with receptor serine-threonine kinases.