Kaech S M, Whitfield C W, Kim S K
Department of Developmental Biology, Stanford University School of Medicine, California 94305, USA.
Cell. 1998 Sep 18;94(6):761-71. doi: 10.1016/s0092-8674(00)81735-3.
In C. elegans, the LET-23 receptor tyrosine kinase is localized to the basolateral membranes of polarized vulval epithelial cells. lin-2, lin-7, and lin-10 are required for basolateral localization of LET-23, since LET-23 is mislocalized to the apical membrane in lin-2, lin-7, and lin-10 mutants. Yeast two-hybrid, in vitro binding, and in vivo coimmunoprecipitation experiments show that LIN-2, LIN-7, and LIN-10 form a protein complex. Furthermore, compensatory mutations in lin-7 and let-23 exhibit allele-specific suppression of apical mislocalization and signaling-defective phenotypes. These results present a mechanism for basolateral localization of LET-23 receptor tyrosine kinase by direct binding to the LIN-2/LIN-7/LIN-10 complex. Each of the binding interactions within this complex is conserved, suggesting that this complex may also mediate basolateral localization in mammals.
在秀丽隐杆线虫中，LET-23受体酪氨酸激酶定位于极化的外阴上皮细胞的基底外侧膜。lin-2、lin-7和lin-10是LET-23基底外侧定位所必需的，因为在lin-2、lin-7和lin-10突变体中，LET-23会错误定位于顶端膜。酵母双杂交、体外结合和体内共免疫沉淀实验表明，LIN-2、LIN-7和LIN-10形成一种蛋白质复合物。此外，lin-7和let-23中的补偿性突变表现出对顶端错误定位和信号缺陷表型的等位基因特异性抑制。这些结果提出了一种通过直接结合LIN-2/LIN-7/LIN-10复合物来实现LET-23受体酪氨酸激酶基底外侧定位的机制。该复合物内的每个结合相互作用都是保守的，这表明该复合物也可能介导哺乳动物中的基底外侧定位。
