Sorting Nexins and Intracellular Protein Trafficking

分选连接蛋白是哺乳动物蛋白质的一个家族，其含有PX结构域，与酵母中正常蛋白质运输所需的几种蛋白质具有密切的同源性。SNX 1和SNX 2是Vps 5 p的同源物，Vps 5 p是一种参与蛋白质从晚期内体到高尔基体的逆行运输的蛋白质。SNX 3是Grd 19 p的直系同源物，Grd 19 p是一种将Kex 2 p等蛋白质保留在高尔基体中所需的蛋白质。SNX 8是Mvp 1 p的同源物，Mvp 1 p是一种与发动蛋白样蛋白（Vps 1 p）相互作用的蛋白质。我们已经获得了几种分选连接蛋白（SNX 1 -4、8和15）的cDNA，并且还获得了含有Vps 5 p的多聚体复合物的几种其他组分的人同源物的cDNA（即，Vps 26 p、Vps 29 p和Vps 35 p）。我们已经证明这些蛋白质中的几种与各种受体酪氨酸激酶（例如，胰岛素、EGF和PDGF的受体），以及瘦素受体的长同种型。此外，我们还利用酵母双杂交系统研究了这些蛋白之间的相互作用。该数据与其中人Vps 35通过提供SNX 1、hVps 26和hVps 29的结合位点而充当多聚体复合物的核心的模型一致。研究正在进行中，以阐明这些蛋白质在哺乳动物细胞内的蛋白质运输中的作用。- 蛋白运输，液泡蛋白分选，内体，溶酶体，高尔基体，胰岛素，瘦素，受体酪氨酸激酶

Sorting nexins are a family of mammalian proteins that contain PX domains with close homology to several proteins that are required for normal protein trafficking in yeast. SNX1 and SNX2 are close homologs of Vps5p, a protein involved in retrograde traffic of proteins from late endosomes to the Golgi. SNX3 is the ortholog of Grd19p, a protein required to retain proteins such as Kex2p in the Golgi. SNX8 is a close homolog of Mvp1p, a protein that interacts with a dynamin-like protein (Vps1p). We have obtained cDNAs for several sorting nexins (SNX1-4, 8, and 15), and also obtained cDNAs for human homologs of several other components of the multimeric complex containing Vps5p (i.e., Vps26p, Vps29p, and Vps35p). We have demonstrated that several of these proteins interact with various receptor tyrosine kinases (e.g., receptors for insulin, EGF, and PDGF) and also with the long isoform of the leptin receptor. In addition, we have used the yeast two hybrid system to characterize the interactions among these proteins. The data are consistent with a model in which human Vps35 serves as the core of a multimeric complex by providing binding sites for SNX1, hVps26, and hVps29. Studies are underway to elucidate the roles of these proteins in protein trafficking within mammalian cells. - protein trafficking, vacuolar protein sorting, endosome, lysosome, golgi, insulin, leptin, receptor tyrosine kinase