Docking Interactions of Hematopoietic Tyrosine Phosphatase with MAP Kinases ERK2 and p38α
Docking Interactions of Hematopoietic Tyrosine Phosphatase with MAP Kinases ERK2 and p38α
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DOI：
10.1021/bi3012725
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发表时间：
2012-10-16
期刊：
影响因子：
2.9
通讯作者：
Ghose, Ranajeet
中科院分区：
文献类型：
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作者：
Piserchio, Andrea;Francis, Dana M.;Ghose, Ranajeet
造血酪氨酸磷酸酶（HePTP）通过使细胞外信号调节激酶（ERK）和p38去磷酸化来调节正交MAP激酶信号级联。HePTP使用保守的N-末端序列基序（D-motif）识别其靶点上的对接位点（D-recruitment site，DRS）。使用溶液核磁共振光谱和等温滴定量热法，我们比较，第一次，对接相互作用的HePTP与ERK 2和p38 α。我们的研究结果表明，ERK 2-HePTP相互作用主要涉及D-基序，而称为激酶特异性基序的连续区域也在p38 α-HePTP相互作用中起着关键作用。两种激酶的D-Motif-DRS相互作用虽然总体上相似，但确实显示出一些特定的差异。
Hematopoietic tyrosine phosphatase (HePTP) regulates orthogonal MAP kinase signaling cascades by dephosphorylating both extracellular signal-regulated kinase (ERK) and p38. HePTP recognizes a docking site (D-recruitment site, DRS) on its targets using a conserved N-terminal sequence motif (D-motif). Using solution nuclear magnetic resonance spectroscopy and isothermal titration calorimetry, we compare, for the first time, the docking interactions of HePTP with ERK2 and p38 alpha. Our results demonstrate that ERK2-HePTP interactions primarily involve the D-motif, while a contiguous region called the kinase specificity motif also plays a key role in p38 alpha-HePTP interactions. D-Motif-DRS interactions for the two kinases, while similar overall, do show some specific differences.