Parks W T, Frank D B, Huff C, Renfrew Haft C, Martin J, Meng X, de Caestecker M P, McNally J G, Reddi A, Taylor S I, Roberts A B, Wang T, Lechleider R J
Laboratory of Cell Regulation and Carcinogenesis, NCI, the Diabetes Branch, NIDDK, National Institutes of Health, Bethesda, Maryland 20892, USA.
J Biol Chem. 2001 Jun 1;276(22):19332-9. doi: 10.1074/jbc.M100606200. Epub 2001 Mar 8.
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 members of the transforming growth factor-beta 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 TbetaRII. Of the type I receptors, SNX6 was found to interact only with inactivated TbetaRI. SNXs 1-4 also interacted with the transforming growth factor-beta 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.
分选连接蛋白（SNX）构成了一类蛋白质家族，与几种酵母蛋白具有同源性，包括Vps5p和Mvp1p，这些蛋白是蛋白质分选到酵母液泡所必需的。有人提出人类SNX1、-2和-4在受体运输中发挥作用，并已证明它们能与几种受体酪氨酸激酶结合，包括表皮生长因子受体、血小板衍生生长因子受体和胰岛素受体，以及瘦素受体的长形式（一种糖蛋白130相关受体）。我们现在描述这个家族的一个新成员SNX6，它与转化生长因子-β家族的受体丝氨酸-苏氨酸激酶成员相互作用。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，发现SNX6与激活素受体IIB（ActRIIB）强烈相互作用，与野生型和激酶缺陷型TβRII突变体的相互作用较弱。在I型受体中，发现SNX6仅与失活的TβRI相互作用。SNX1-4也与转化生长因子-β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。在SNX-1、-2、-4和-6之间也观察到强烈的异源相互作用，这表明在体内形成了寡聚体复合物。这些发现是SNX分子家族与受体丝氨酸-苏氨酸激酶关联的首个证据。
