SH结构域(Src homology domain)是一种真核生物蛋白结构域，能够与受体酪氨酸激酶磷酸化残基紧密结合,从而形成多蛋白的复合物来进行信号转导。SH3结构域是最初在Src（一种癌基因）的研究中鉴定到的蛋白组件，它能够识别富含脯氨酸和疏水残基的蛋白质并与之结合,从而介导蛋白与蛋白的相互作用，SH3结构域参与了多种细胞内生化反应，包括信号转导、细胞增殖及细胞运动。
之前的研究表明，络氨酸磷酸化对SH3结构域的活性调节具有重要作用。近日，来自布拉格查理大学的研究人员阐明了该作用，并发现了SH3结构域内重要的序列模体ALYD(Y/F)。
利用PhosphoSite Plus数据库，他们发现，到目前为止已经有超过100种不同的络氨酸磷酸化作用发生在SH3结构域内20个不同的位点。
c–Src Tyr90是目前研究得最频繁的SH3结构域的磷酸化位点。通过比较络氨酸周围的序列，他们发现了一个重要的序列模体ALYD(Y/F)。研究表明，这种模体存在于约15%的人SH3结构域，其结构较为保守。
进一步研究发现，SH3结构域及其它接头蛋白（如SH2或是WW结构域）络氨酸的磷酸化比丝氨酸或者是苏氨酸的磷酸化更为丰富。
络氨酸磷酸化是调节接头结构域（adaptor domains）活性的一种重要机制。络氨酸的磷酸化能够促进信号蛋白通过SH2或PTB结构域来相互作用，但是SH3结构域的磷酸化作用却不然，它反而妨碍了信号分子之间的相互作用。研究人员Marian Novotny表示，这种络氨酸磷酸化的调节作用很有可能是因为磷酸盐及其电荷能够干扰信号分子与SH3结构域内多聚脯氨酸的结合。（生物谷Deepblue编译）
doi: 10.1371/journal.pone.0036310
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SH3 Domain Tyrosine Phosphorylation – Sites, Role and Evolution
Zuzana Tatárová, Jan Brábek, Daniel Rsel, Marian Novotny.
SH3 domains are eukaryotic protein domains that participate in a plethora of cellular processes including signal transduction, proliferation, and cellular movement. Several studies indicate that tyrosine phosphorylation could play a significant role in the regulation of SH3 domains.To explore the incidence of the tyrosine phosphorylation within SH3 domains we queried the PhosphoSite Plus database of phosphorylation sites. Over 100 tyrosine phosphorylations occurring on 20 different SH3 domain positions were identified. The tyrosine corresponding to c–Src Tyr-90 was by far the most frequently identified SH3 domain phosphorylation site. A comparison of sequences around this tyrosine led to delineation of a preferred sequence motif ALYD(Y/F).This motif is present in about 15% of human SH3 domains and is structurally well conserved. We further observed that tyrosine phosphorylation is more abundant than serine or threonine phosphorylation within SH3 domains and other adaptor domains, such as SH2 or WW domains.Tyrosine phosphorylation could represent an important regulatory mechanism of adaptor domains.While tyrosine phosphorylation typically promotes signaling protein interactions via SH2 or PTB domains, its role in SH3 domains is the opposite - it blocks or prevents interactions.The regulatory function of tyrosine phosphorylation is most likely achieved by the phosphate moiety and its charge interfering with binding of polyproline helices of SH3 domain interacting partners.
