底物蛋白上的多个对接位点形成一个模块化系统，介导ERK丝裂原活化蛋白激酶的识别。
Multiple docking sites on substrate proteins form a modular system that mediates recognition by ERK MAP kinase.
作者信息
Jacobs D, Glossip D, Xing H, Muslin A J, Kornfeld K
机构信息
Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis, Missouri 63110 USA.
出版信息
Genes Dev. 1999 Jan 15;13(2):163-75.
Abstract
MAP kinases phosphorylate specific groups of substrate proteins. Here we show that the amino acid sequence FXFP is an evolutionarily conserved docking site that mediates ERK MAP kinase binding to substrates in multiple protein families. FXFP and the D box, a different docking site, form a modular recognition system, as they can function independently or in combination. FXFP is specific for ERK, whereas the D box mediates binding to ERK and JNK MAP kinase, suggesting that the partially overlapping substrate specificities of ERK and JNK result from recognition of shared and unique docking sites. These findings enabled us to predict new ERK substrates and design peptide inhibitors of ERK that functioned in vitro and in vivo.
摘要
丝裂原活化蛋白激酶（MAP激酶）使特定的底物蛋白基团发生磷酸化。我们在此表明，氨基酸序列FXFP是一个进化上保守的对接位点，它介导细胞外信号调节激酶（ERK）MAP激酶与多个蛋白质家族中的底物结合。FXFP和另一个不同的对接位点D框形成了一个模块化识别系统，因为它们可以独立发挥作用或联合发挥作用。FXFP对ERK具有特异性，而D框介导与ERK和应激活化蛋白激酶（JNK）MAP激酶的结合，这表明ERK和JNK部分重叠的底物特异性是由对共享和独特对接位点的识别所致。这些发现使我们能够预测新的ERK底物，并设计出在体外和体内均起作用的ERK肽抑制剂。
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