Hoskins R, Hajnal A F, Harp S A, Kim S K
Department of Developmental Biology, Stanford University Medical School, CA 94305, USA.
Development. 1996 Jan;122(1):97-111. doi: 10.1242/dev.122.1.97.
The lin-2 gene is required for the induction of the Caenorhabditis elegans vulva. Vulval development is initiated by a signal from the anchor cell that is transduced by a receptor tyrosine kinase/Ras pathway. We show that lin-2 acts in the vulval precursor cell P6.p, downstream of lin-3 EGF and upstream of let-60 ras, to allow expression of the 1 degrees cell fate. lin-2 encodes a protein of relative molecular mass 109,000 (LIN-2A) with regions of similarity to CaM kinase II and membrane-associated guanylate kinases. Mutant lin-2 transgenes designed to lack either protein kinase or guanylate kinase activity are functional, indicating that LIN-2A has a structural rather than an enzymatic role in vulval induction. Most or all identified membrane-associated guanylate kinases are components of cell junctions, including vertebrate tight junctions and arthropod septate junctions in epithelia. Thus, LIN-2A may be a component of the cell junctions of the epithelial vulval precursor cells that is required for signaling by the receptor tyrosine kinase LET-23. We propose that LIN-2A is required for the localization of one or more signal transduction proteins (such as LET-23) to either the basal membrane domain or the cell junctions, and that mislocalization of signal transduction proteins in lin-2 mutants interferes with vulval induction.
lin-2基因是秀丽隐杆线虫外阴诱导所必需的。外阴发育由来自锚定细胞的信号启动，该信号通过受体酪氨酸激酶/Ras途径进行转导。我们发现，lin-2在1°细胞命运表达所需的外阴前体细胞P6.p中发挥作用，位于lin-3 EGF的下游和let-60 ras的上游。lin-2编码一种相对分子质量为109,000的蛋白质（LIN-2A），其具有与钙调蛋白激酶II和膜相关鸟苷酸激酶相似的区域。设计为缺乏蛋白激酶或鸟苷酸激酶活性的突变lin-2转基因具有功能，这表明LIN-2A在外阴诱导中具有结构作用而非酶促作用。大多数或所有已鉴定的膜相关鸟苷酸激酶都是细胞连接的组成部分，包括上皮细胞中的脊椎动物紧密连接和节肢动物分隔连接。因此，LIN-2A可能是上皮外阴前体细胞连接的一个组成部分，是受体酪氨酸激酶LET-23信号传导所必需的。我们提出，LIN-2A是一种或多种信号转导蛋白（如LET-23）定位于基底膜结构域或细胞连接所必需的，并且lin-2突变体中信号转导蛋白的错误定位会干扰外阴诱导。
