Signaling properties of a non-metazoan Src kinase and the evolutionary history of Src negative regulation
Signaling properties of a non-metazoan Src kinase and the evolutionary history of Src negative regulation
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DOI：
10.1074/jbc.m800002200
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发表时间：
2008-05-30
影响因子：
4.8
通讯作者：
Miller, W. Todd
中科院分区：
文献类型：
--
作者：
Li, Wanqing;Young, Susan L.;Miller, W. Todd
Choanoflagellates，与后生动物密切相关的单细胞生物，具有细胞粘附和信号蛋白，以前被认为是动物所特有的，这表明这些成分可能在后生动物多细胞性的进化中发挥了作用。我们已经克隆，表达和纯化的非受体酪氨酸激酶MbSrc 1从cho-anoflagellate Monosiga brevicollis。该激酶具有与哺乳动物Src激酶相同的结构域排列，我们发现单个Src同源3（SH 3），SH 2和催化结构域具有与哺乳动物对应物相似的功能。与哺乳动物的c-Src相反，MbSrc 1的SH 2和催化结构域似乎没有功能性偶联。我们克隆并表达了M. c-Src C-末端激酶（MbCsk）的短颈霉同源物，并显示其磷酸化MbSrc 1的C末端，但这种磷酸化不会抑制MbSrc达到与哺乳动物Src/Csk对中所见的相同程度。因此，Src自抑制可能是最近在后生动物谱系中进化的，并且它可能在后生动物中细胞间信号的建立中发挥了作用。
Choanoflagellates, unicellular organisms that are closely related to metazoans, possess cell adhesion and signaling proteins previously thought to be unique to animals, suggesting that these components may have played roles in the evolution of metazoan multicellularity. We have cloned, expressed, and purified the nonreceptor tyrosine kinase MbSrc1 from the cho-anoflagellate Monosiga brevicollis. The kinase has the same domain arrangement as mammalian Src kinases, and we find that the individual Src homology 3 (SH3), SH2, and catalytic domains have similar functions to their mammalian counterparts. In contrast to mammalian c-Src, the SH2 and catalytic domains of MbSrc1 do not appear to be functionally coupled. We cloned and expressed the M. brevicollis homolog of c-Src C-terminal kinase (MbCsk) and showed that it phosphorylates the C terminus of MbSrc1, yet this phosphorylation does not inhibit MbSrc to the same degree seen in the mammalian Src/Csk pair. Thus, Src autoinhibition likely evolved more recently within the metazoan lineage, and it may have played a role in the establishment of intercellular signaling in metazoans.