A quantitative study of the recruitment potential of all intracellular tyrosine residues on EGFR, FGFR1 and IGF1R
A quantitative study of the recruitment potential of all intracellular tyrosine residues on EGFR, FGFR1 and IGF1R
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DOI：
10.1039/b801018h
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发表时间：
2008-01-01
影响因子：
--
通讯作者：
MacBeath, Gavin
中科院分区：
文献类型：
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作者：
Kaushansky, Alexis;Gordus, Andrew;MacBeath, Gavin
受体酪氨酸激酶通过将细胞内信号蛋白募集到酪氨酸磷酸化位点来传递和处理细胞外信号。使用包含几乎所有人类SH2和PTB结构域的蛋白质微阵列，我们使用从每个受体上的每个细胞内酪氨酸残基衍生的磷酸肽，无论它们是否在体内磷酸化，为三种已被充分研究的受体（EGFR， FGFR1和IGF1R）生成了定量的蛋白质相互作用图。我们发现，总的来说，来自酪氨酸磷酸化的生理位点的肽比来自非生理位点的肽能结合更多的SH2或PTB结构域，这支持了激酶和相互作用结构域共同进化的观点，并表明新位点的出现主要是通过选择有利于有利的相互作用，而不是通过选择不利于不利的相互作用。我们还发现在这三种受体的招募谱中有大量的定性重叠，这表明它们不同的生物学效应至少部分来自于它们对所招募蛋白质的亲和力的定量差异。
Receptor tyrosine kinases transmit and process extracellular cues by recruiting intracellular signaling proteins to sites of tyrosine phosphorylation. Using protein microarrays comprising virtually every human SH2 and PTB domain, we generated quantitative protein interaction maps for three well-studied receptors - EGFR, FGFR1 and IGF1R - using phosphopeptides derived from every intracellular tyrosine residue on each receptor, regardless of whether or not they are phosphorylated in vivo. We found that, in general, peptides derived from physiological sites of tyrosine phosphorylation bind to substantially more SH2 or PTB domains than do peptides derived from nonphysiological sites, supporting the idea that kinases and interaction domains co-evolve and suggesting that new sites arise predominantly through selection favoring advantageous interactions, rather than through selection disfavoring unwanted interactions. We also found substantial qualitative overlap in the recruitment profiles of these three receptors, suggesting that their different biological effects arise, at least in part, from quantitative differences in their affinities for the proteins they recruit.