Henderson S T, Gao D, Christensen S, Kimble J
Howard Hughes Medical Institute, University of Wisconsin-Madison 53706, USA.
Mol Biol Cell. 1997 Sep;8(9):1751-62. doi: 10.1091/mbc.8.9.1751.
The LAG-2 membrane protein is a putative signaling ligand for the LIN-12 and GLP-1 receptors of Caenorhabditis elegans. LAG-2, like its Drosophila homologues Delta and Serrate, acts in a conserved signal transduction pathway to regulate cell fates during development. In this article, we investigate the functional domains of LAG-2. For the most part, mutants were constructed in vitro and assayed for activity in transgenic animals. We find a functional role for all major regions except one. Within the extracellular domain, the N-terminal region, which bears no known motif, and the DSL domain are both required. By contrast, the region bearing epidermal growth factor-like repeats can be deleted with no apparent reduction in rescuing activity. The intracellular region is not required for activity but instead plays a role in down-regulating LAG-2 function. Finally, membrane association is critical for mutant rescue.
LAG - 2膜蛋白是秀丽隐杆线虫LIN - 12和GLP - 1受体的一种假定信号配体。LAG - 2与其果蝇同源物Delta和Serrate一样，在保守的信号转导途径中发挥作用，以在发育过程中调节细胞命运。在本文中，我们研究了LAG - 2的功能结构域。大部分情况下，突变体是在体外构建的，并在转基因动物中检测其活性。我们发现除了一个区域外，所有主要区域都具有功能作用。在细胞外结构域中，没有已知基序的N端区域和DSL结构域都是必需的。相比之下，带有表皮生长因子样重复序列的区域可以缺失，而拯救活性没有明显降低。细胞内区域对于活性不是必需的，而是在下调LAG - 2功能中发挥作用。最后，膜结合对于突变体拯救至关重要。
