Forrester W C, Dell M, Perens E, Garriga G
Department of Molecular and Cell Biology, University of California, Berkeley 94720, USA.
Nature. 1999 Aug 26;400(6747):881-5. doi: 10.1038/23722.
Ror kinases are a family of orphan receptors with tyrosine kinase activity that are related to muscle specific kinase (MuSK), a receptor tyrosine kinase that assembles acetylcholine receptors at the neuromuscular junction. Although the functions of Ror kinases are unknown, similarities between Ror and MuSK kinases have led to speculation that Ror kinases regulate synaptic development. Here we show that the Caenorhabditis elegans gene cam-1 encodes a member of the Ror kinase family that guides migrating cells and orients the polarity of asymmetric cell divisions and axon outgrowth. We find that tyrosine kinase activity is required for some of the functions of CAM-1, but not for its role in cell migration. CAM-1 is expressed in cells that require its function, and acts cell autonomously in migrating neurons. Overexpression and loss of cam-1 function result in reciprocal cell-migration phenotypes, indicating that levels of CAM-1 influence the final positions of migrating cells. Our results raise the possibility that Ror kinases regulate cell motility and asymmetric cell division in organisms as diverse as nematodes and mammals.
Ror激酶是一类具有酪氨酸激酶活性的孤儿受体家族,与肌肉特异性激酶(MuSK)相关,MuSK是一种受体酪氨酸激酶,可在神经肌肉接头处组装乙酰胆碱受体。尽管Ror激酶的功能尚不清楚,但Ror激酶与MuSK激酶之间的相似性引发了人们对Ror激酶调节突触发育的猜测。在此,我们表明秀丽隐杆线虫基因cam-1编码Ror激酶家族的一个成员,该成员可引导迁移细胞并确定不对称细胞分裂和轴突生长的极性。我们发现酪氨酸激酶活性对于CAM-1的某些功能是必需的,但对于其在细胞迁移中的作用并非必需。CAM-1在需要其功能的细胞中表达,并在迁移的神经元中自主发挥作用。cam-1功能的过表达和缺失会导致相反的细胞迁移表型,表明CAM-1的水平会影响迁移细胞的最终位置。我们的结果增加了一种可能性,即Ror激酶在包括线虫和哺乳动物在内的多种生物中调节细胞运动性和不对称细胞分裂。