Evidence for convergent evolution in the signaling properties of a choanoflagellate tyrosine kinase.
Evidence for convergent evolution in the signaling properties of a choanoflagellate tyrosine kinase.
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DOI：
10.1021/bi9000672
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发表时间：
2009-06-16
期刊：
影响因子：
2.9
通讯作者：
Miller, W. Todd
中科院分区：
文献类型：
--
作者：
Li, Wanqing;Scarlata, Suzanne;Miller, W. Todd
直到最近，磷酸酪氨酸信号被认为仅限于多细胞动物。令人惊讶的是，单细胞的choanoflagellate Monosiga brevicollis包含的酪氨酸激酶的数量和多样性超过了任何后生动物，包括人类。许多M。短颈菌属酪氨酸激酶具有多细胞动物中不存在的信号传导结构域的组合。一种这样的激酶，Src样蛋白MbSrc 4，含有一个脂质结合C2结构域的N-末端保守的SH 3-SH 2-激酶结构域。在这里，我们报告说，酶是高度活跃的酪氨酸激酶和C2，SH 3和SH 2结构域的靶向功能是类似的哺乳动物同行。C2结构域的膜结合活性在功能上等同于c-Src的豆蔻酰化信号，这表明它是趋同进化的一个例子。当在哺乳动物细胞中表达时，全长MbSrc 4显示对内源性蛋白质的低活性，并且在报告基因测定中它不能在功能上替代哺乳动物c-Src。MbSrc 4 C2结构域的去除导致细胞蛋白的磷酸化增加。因此，与相关的M.短颈霉Src样激酶MbSrc 1、MbSrc 4不能正确地靶向哺乳动物Src底物，表明C2结构域在M.短颈信号
Until recently, phosphotyrosine signaling was thought to be restricted to multicellular animals. Surprisingly, the unicellular choanoflagellate Monosiga brevicollis contains a number and diversity of tyrosine kinases that exceeds that of any metazoan, including humans. Many of these M. brevicollis tyrosine kinases possess combinations of signaling domains that do not occur in metazoans. One such kinase, the Src-like protein MbSrc4, contains a lipid-binding C2 domain N-terminal to the conserved SH3-SH2-kinase domains. Here, we report that the enzyme is highly active as a tyrosine kinase and that the targeting functions of the C2, SH3, and SH2 domains are similar to the mammalian counterparts. The membrane-binding activity of the C2 domain is functionally equivalent to the myristoylation signal of c-Src, suggesting that it is an example of convergent evolution. When expressed in mammalian cells, full-length MbSrc4 displays low activity toward endogenous proteins, and it cannot functionally substitute for mammalian c-Src in a reporter gene assay. Removal of the MbSrc4 C2 domain leads to increased phosphorylation of cellular proteins. Thus, in contrast to the related M. brevicollis Src-like kinase MbSrc1, MbSrc4 is not targeted properly to mammalian Src substrates, suggesting that the C2 domain plays a specific role in M. brevicollis signaling.
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DOI：
10.1073/pnas.0801314105
发表时间：
2008-07-15
影响因子：
11.1
作者：
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通讯作者：
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影响因子：
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作者：
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Miller, WT
影响因子：
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作者：
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通讯作者：
Miller, W. Todd
DOI：
10.1073/pnas.0600021103
发表时间：
2006-08-08
影响因子：
11.1
作者：
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通讯作者：
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