Lin D, Edwards A S, Fawcett J P, Mbamalu G, Scott J D, Pawson T
Program in Molecular Biology and Cancer, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, Ontario M5G 1X5, Canada.
Nat Cell Biol. 2000 Aug;2(8):540-7. doi: 10.1038/35019582.
Cellular asymmetry is critical for the development of multicellular organisms. Here we show that homologues of proteins necessary for asymmetric cell division in Caenorhabditis elegans associate with each other in mammalian cells and tissues. mPAR-3 and mPAR-6 exhibit similar expression patterns and subcellular distributions in the CNS and associate through their PDZ (PSD-95/Dlg/ZO-1) domains. mPAR-6 binds to Cdc42/Rac1 GTPases, and mPAR-3 and mPAR-6 bind independently to atypical protein kinase C (aPKC) isoforms. In vitro, mPAR-3 acts as a substrate and an inhibitor of aPKC. We conclude that mPAR-3 and mPAR-6 have a scaffolding function, coordinating the activities of several signalling proteins that are implicated in mammalian cell polarity.
细胞不对称性对于多细胞生物的发育至关重要。在此我们表明,秀丽隐杆线虫中不对称细胞分裂所必需的蛋白质同源物在哺乳动物细胞和组织中相互关联。mPAR - 3和mPAR - 6在中枢神经系统中表现出相似的表达模式和亚细胞分布,并通过它们的PDZ(PSD - 95/Dlg/ZO - 1)结构域相互关联。mPAR - 6与Cdc42/Rac1 GTP酶结合,而mPAR - 3和mPAR - 6独立地与非典型蛋白激酶C(aPKC)亚型结合。在体外,mPAR - 3作为aPKC的底物和抑制剂。我们得出结论,mPAR - 3和mPAR - 6具有支架功能,协调参与哺乳动物细胞极性的几种信号蛋白的活性。