Functional development of Src tyrosine kinases during evolution from a unicellular ancestor to multicellular animals
Functional development of Src tyrosine kinases during evolution from a unicellular ancestor to multicellular animals
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DOI：
10.1073/pnas.0600021103
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发表时间：
2006-08-08
影响因子：
11.1
通讯作者：
Okada, Masato
中科院分区：
文献类型：
--
作者：
Segawa, Yuko;Suga, Hiroshi;Okada, Masato
酪氨酸激酶Src家族在调节多细胞动物特有的细胞功能中起关键作用，包括细胞-细胞相互作用、细胞-基质粘附和细胞迁移。为了研究从单细胞祖先到多细胞动物进化过程中Src激酶的功能变化，我们从单细胞后囊鞭毛虫Monosiga ovata和原始多细胞海绵Ephydatia fluviatilis中鉴定了Src同源物。在此，我们发现src基因家族及其C-末端Src激酶（Csk）介导的调控系统已经在单细胞M.单细胞Src相对于多细胞Src具有独特的特征：它可以在负调控位点被Csk磷酸化，但即使在磷酸化形式下仍表现出相当大的活性。M. ovata和E. fluviatilisSrc同源物揭示了激酶结构域的结构改变是M.奥瓦塔湾当在脊椎动物成纤维细胞中表达时，M. ovata Src可以诱导细胞转化，而与Csk的存在无关。这些发现表明，稳定的Csk介导的负调控所需的Src结构在单细胞M中仍然是不成熟的。而Src稳定负调控的发展可能与动物多细胞性的进化有关。
The Src family of tyrosine kinases play pivotal roles in regulating cellular functions characteristic of multicellular animals, including cell-cell interactions, cell-substrate adhesion, and cell migration. To investigate the functional alteration of Src kinases during evolution from a unicellular ancestor to multicellular animals, we characterized Src orthologs from the unicellular choanoflagellate Monosiga ovata and the primitive multicellular sponge Ephydatia fluviatilis. Here, we show that the src gene family and its C-terminal Src kinase (Csk)-mediated regulatory system already were established in the unicellular M. ovata and that unicellular Src has unique features relative to multicellular Src: It can be phosphorylated by Csk at the negative regulatory site but still exhibits substantial activity even in the phosphorylated form. Analyses of chimera molecules between M. ovata and E. fluviatilis Src orthologs reveal that structural alterations in the kinase domain are responsible for the unstable negative regulation of M. ovata Src. When expressed in vertebrate fibroblasts, M. ovata Src can induce cell transformation irrespective of the presence of Csk. These findings suggest that a structure of Src required for the stable Csk-mediated negative regulation still is immature in the unicellular M. ovata and that the development of stable negative regulation of Src may correlate with the evolution of multicellularity in animals.