Faculty of Life and Environmental Sciences, Prefectural University of Hiroshima, 727-0023, Shobara, Hiroshima, Japan.
Department of Physiology and Biophysics, Stony Brook University, Stony Brook, NY, 11794, USA.
Sci Rep. 2018 Mar 29;8(1):5362. doi: 10.1038/s41598-018-23721-8.
Creolimax fragrantissima is a member of the ichthyosporean clade, the earliest branching holozoan lineage. The kinome of Creolimax is markedly reduced as compared to those of metazoans. In particular, Creolimax possesses a single non-receptor tyrosine kinase: CfrSrc, the homolog of c-Src kinase. CfrSrc is an active tyrosine kinase, and it is expressed throughout the lifecycle of Creolimax. In animal cells, the regulatory mechanism for Src involves tyrosine phosphorylation at a C-terminal site by Csk kinase. The lack of Csk in Creolimax suggests that a different mode of negative regulation must exist for CfrSrc. We demonstrate that CfrPTP-3, one of the 7 tyrosine-specific phosphatases (PTPs) in Creolimax, suppresses CfrSrc activity in vitro and in vivo. Transcript levels of CfrPTP-3 and two other PTPs are significantly higher than that of CfrSrc in the motile amoeboid and sessile multinucleate stages of the Creolimax life cycle. Thus, in the context of a highly reduced kinome, a pre-existing PTP may have been co-opted for the role of Src regulation. Creolimax represents a unique model system to study the adaptation of tyrosine kinase signaling and regulatory mechanisms.
香丽鱼丽体虫是鱼生动物分支中最早的一个真后生动物谱系的一员。与后生动物相比，丽体虫的激酶组明显减少。特别是，丽体虫只拥有一个非受体酪氨酸激酶：CfrSrc，它是 c-Src 激酶的同源物。CfrSrc 是一种活性的酪氨酸激酶，它在丽体虫的整个生命周期中都有表达。在动物细胞中，Src 的调节机制涉及 Csk 激酶在 C 端位点的酪氨酸磷酸化。丽体虫中缺乏 Csk，表明 CfrSrc 必须存在不同的负调控模式。我们证明，丽体虫中的 7 种酪氨酸特异性磷酸酶（PTPs）之一 CfrPTP-3 在体外和体内均能抑制 CfrSrc 的活性。在丽体虫生命周期的运动性阿米巴虫和固着多核阶段，CfrPTP-3 和另外两种 PTP 的转录水平明显高于 CfrSrc。因此，在高度简化的激酶组的背景下，先前存在的 PTP 可能被重新用于 Src 调节的作用。丽体虫代表了一个独特的模型系统，可用于研究酪氨酸激酶信号转导和调节机制的适应性。
