The SH2 domain-containing proteins in 21 species establish the provenance and scope of phosphotyrosine signaling in eukaryotes.

The SH2 domain-containing proteins in 21 species establish the provenance and scope of phosphotyrosine signaling in eukaryotes.
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DOI:
10.1126/scisignal.2002105
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发表时间:
2011-12-06
期刊:
影响因子:
7.3
通讯作者:
Nash PD
Nash PD
中科院分区:
生物学1区
文献类型:
--
作者:
Liu BA;Shah E;Jablonowski K;Stergachis A;Engelmann B;Nash PD

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Src同源2(SH 2)结构域参与后生动物信号转导,作为调节蛋白质-蛋白质与酪氨酸磷酸化底物相互作用的主要介质。在这里,我们描述的起源和进化的SH 2结构域蛋白的序列分析从21个真核生物的基础单细胞真核生物,SH 2结构域首次出现,通过多细胞动物和越来越复杂的后生动物。在我们的研究结果的基础上,SH 2结构域和磷酸酪氨酸信号出现在早期Unikonta,和SH 2结构域的数量扩大的choanoflagellate和后生动物的谱系与酪氨酸激酶的发展,导致磷酸酪氨酸信号在早期多细胞动物的快速阐述。我们的研究结果还表明,SH 2结构域共同进化和结构域的数量扩大旁边的蛋白酪氨酸激酶和酪氨酸磷酸酶,从而耦合磷酸酪氨酸信号下游信号网络。基因复制与结构域的获得或丢失相结合,产生了新的含SH 2的蛋白质,这些蛋白质在磷酸酪氨酸信号传导中起作用,这可能有助于后生动物的多样性和复杂性。我们发现SH 2结构域蛋白内部和之间的分子内和分子间相互作用随着生物体复杂性的增加而沿着增加,并可能起到产生更高度连接和更强大的磷酸酪氨酸信号网络的作用。
The Src homology 2 (SH2) domains are participants in metazoan signal transduction, acting as primary mediators for regulated protein-protein interactions with tyrosine-phosphorylated substrates. Here, we describe the origin and evolution of SH2 domain proteins by means of sequence analysis from 21 eukaryotic organisms from the basal unicellular eukaryotes, where SH2 domains first appeared, through the multicellular animals and increasingly complex metazoans. On the basis of our results, SH2 domains and phosphotyrosine signaling emerged in the early Unikonta, and the numbers of SH2 domains expanded in the choanoflagellate and metazoan lineages with the development of tyrosine kinases, leading to rapid elaboration of phosphotyrosine signaling in early multicellular animals. Our results also indicated that SH2 domains coevolved and the number of the domains expanded alongside protein tyrosine kinases and tyrosine phosphatases, thereby coupling phosphotyrosine signaling to downstream signaling networks. Gene duplication combined with domain gain or loss produced novel SH2-containing proteins that function within phosphotyrosine signaling, which likely have contributed to diversity and complexity in metazoans. We found that intra- and intermolecular interactions within and between SH2 domain proteins increased in prevalence along with organismal complexity and may function to generate more highly connected and robust phosphotyrosine signaling networks.
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