Gao D, Kimble J
Department of Biochemistry, University of Wisconsin-Madison 53706, USA.
Proc Natl Acad Sci U S A. 1995 Oct 10;92(21):9839-42. doi: 10.1073/pnas.92.21.9839.
The homologous LAG-2 and APX-1 membrane proteins are putative signaling ligands in the GLP-1/LIN-12 signal-transduction pathway in Caenorhabditis elegans. Normally, LAG-2 and APX-1 mediate distinct cell interactions. Here, we demonstrate that APX-1, which normally interacts with GLP-1 in the early embryo, can substitute for LAG-2 throughout development. When expressed under control of the lag-2 promoter, an apx-1 cDNA can completely rescue a lag-2 null mutant. To substitute for LAG-2, APX-1 must be able to interact with both GLP-1 and LIN-12 receptors and to mediate a variety of cell interactions during development. Therefore, APX-1 and LAG-2 are essentially equivalent in their ability to influence receptor activity. On the basis of this result, we suggest that the existence of multiple-signaling ligands in the LIN-12/GLP-1 signal transduction pathway does not reflect the evolution of functionally distinct proteins but rather the imposition of distinct controls of gene expression upon functionally similar proteins. Finally, we propose that the specification of distinct cell fates by the LIN-12/GLP-1 signal-transduction pathway relies on activities functioning downstream of the ligand and receptor, rather than on specific ligand-receptor interactions.
同源的LAG-2和APX-1膜蛋白是秀丽隐杆线虫GLP-1/LIN-12信号转导途径中假定的信号配体。正常情况下，LAG-2和APX-1介导不同的细胞相互作用。在此，我们证明，通常在早期胚胎中与GLP-1相互作用的APX-1在整个发育过程中可以替代LAG-2。当在lag-2启动子的控制下表达时，一个apx-1 cDNA可以完全拯救lag-2缺失突变体。为了替代LAG-2，APX-1必须能够与GLP-1和LIN-12受体相互作用，并在发育过程中介导多种细胞相互作用。因此，APX-1和LAG-2在影响受体活性的能力上基本相当。基于这一结果，我们认为LIN-12/GLP-1信号转导途径中多个信号配体的存在并不反映功能不同的蛋白质的进化，而是反映了对功能相似的蛋白质施加了不同的基因表达控制。最后，我们提出LIN-12/GLP-1信号转导途径对不同细胞命运的特化依赖于配体和受体下游起作用的活性，而不是依赖于特定的配体-受体相互作用。
