SH結(jié)構(gòu)域(Src homology domain)是一種真核生物蛋白結(jié)構(gòu)域,，能夠與受體酪氨酸激酶磷酸化殘基緊密結(jié)合,從而形成多蛋白的復(fù)合物來進行信號轉(zhuǎn)導(dǎo),。SH3結(jié)構(gòu)域是最初在Src（一種癌基因）的研究中鑒定到的蛋白組件，它能夠識別富含脯氨酸和疏水殘基的蛋白質(zhì)并與之結(jié)合,從而介導(dǎo)蛋白與蛋白的相互作用,，SH3結(jié)構(gòu)域參與了多種細胞內(nèi)生化反應(yīng),，包括信號轉(zhuǎn)導(dǎo)、細胞增殖及細胞運動,。
之前的研究表明,，絡(luò)氨酸磷酸化對SH3結(jié)構(gòu)域的活性調(diào)節(jié)具有重要作用。近日,，來自布拉格查理大學(xué)的研究人員闡明了該作用,，并發(fā)現(xiàn)了SH3結(jié)構(gòu)域內(nèi)重要的序列模體ALYD(Y/F)。
利用PhosphoSite Plus數(shù)據(jù)庫,，他們發(fā)現(xiàn),，到目前為止已經(jīng)有超過100種不同的絡(luò)氨酸磷酸化作用發(fā)生在SH3結(jié)構(gòu)域內(nèi)20個不同的位點,。
c–Src Tyr90是目前研究得最頻繁的SH3結(jié)構(gòu)域的磷酸化位點。通過比較絡(luò)氨酸周圍的序列,，他們發(fā)現(xiàn)了一個重要的序列模體ALYD(Y/F),。研究表明，這種模體存在于約15%的人SH3結(jié)構(gòu)域,，其結(jié)構(gòu)較為保守,。
進一步研究發(fā)現(xiàn)，SH3結(jié)構(gòu)域及其它接頭蛋白（如SH2或是WW結(jié)構(gòu)域）絡(luò)氨酸的磷酸化比絲氨酸或者是蘇氨酸的磷酸化更為豐富,。
絡(luò)氨酸磷酸化是調(diào)節(jié)接頭結(jié)構(gòu)域（adaptor domains）活性的一種重要機制,。絡(luò)氨酸的磷酸化能夠促進信號蛋白通過SH2或PTB結(jié)構(gòu)域來相互作用，但是SH3結(jié)構(gòu)域的磷酸化作用卻不然,，它反而妨礙了信號分子之間的相互作用,。研究人員Marian Novotny表示，這種絡(luò)氨酸磷酸化的調(diào)節(jié)作用很有可能是因為磷酸鹽及其電荷能夠干擾信號分子與SH3結(jié)構(gòu)域內(nèi)多聚脯氨酸的結(jié)合,。（生物谷Deepblue編譯）
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.
