Direct binding of eps8 to the juxtamembrane domain of EGFR is phosphotyrosine- and SH2-independent.
Direct binding of eps8 to the juxtamembrane domain of EGFR is phosphotyrosine- and SH2-independent.
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发表时间：
1995-02
期刊：
影响因子：
8
通讯作者：
P. Castagnino;Z. Biesová;W. Wong;F. Fazioli;G. Gill;P. P. Di Fiore-P.
中科院分区：
文献类型：
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作者：
P. Castagnino;Z. Biesová;W. Wong;F. Fazioli;G. Gill;P. P. Di Fiore-P.
几种信号转导器通过其 SH2 结构域与受体酪氨酸激酶 (RTK) 中存在的含磷酸酪氨酸的基序结合。然而，表皮生长因子受体 (EGFR) 和相关 erbB-2 蛋白的近膜区域虽然在促有丝分裂信号传导中很重要，但缺乏明显的酪氨酸磷酸化位点，这表明存在其他形式的受体-转导器相互作用。 p97eps8 是研究此类关联的候选者，它是最近描述的 RTK 底物。 p97eps8 被多种 RTK 磷酸化，在体内与 EGFR 结合，并且在过度表达后增强 EGFR 介导的有丝分裂信号的转导。在此，我们报道eps8通过与SH2结构域不相似的结构域以及不需要存在磷酸酪氨酸残基的机制直接结合EGFR的近膜区域。因此，EGFR 和 eps8 之间的物理关联代表了 RTK 与其底物之间的新型相互作用。
Several signal transducers bind through their SH2 domains to phosphotyrosine-containing motifs present in receptor tyrosine kinases (RTKs). However, the juxtamembrane regions of the epidermal growth factor receptor (EGFR) and of the related erbB-2 protein, while important in mitogenic signaling, lack demonstrable tyrosine phosphorylation sites, suggesting that other modalities of receptor-transducer interactions exist. A candidate for investigating this type of association is p97eps8, a recently described substrate for RTKs. p97eps8 is phosphorylated by several RTKs, associates with EGFR in vivo and, upon overexpression, enhances the transduction of EGFR-mediated mitogenic signals. Here we report that eps8 binds directly to the juxtamembrane region of EGFR through a domain that does not bear resemblance to SH2 domains and by a mechanism that does not require the presence of phosphotyrosine residues. Thus, the physical association between EGFR and eps8 represents a novel interaction between RTKs and their substrates.