Kallunki T, Deng T, Hibi M, Karin M
Department of Pharmacology, School of Medicine, University of California, San Diego, La Jolla 92093-0636, USA.
Cell. 1996 Nov 29;87(5):929-39. doi: 10.1016/s0092-8674(00)81999-6.
Structurally related serine/threonine kinases recognize similar phosphoacceptor peptides in vitro yet in vivo, they phosphorylate distinct substrates. To understand the basis for this specificity, we studied the interaction between the Jun kinases (JNKs) and Jun proteins. JNKs phosphorylate c-Jun very efficiently, JunD less efficiently, but they do not phosphorylate JunB. Effective JNK substrates require a separate docking site and specificity-conferring residues flanking the phosphoacceptor. The docking site increases the efficiency and specificity of the phosphorylation reaction. JunB has a functional JNK docking site but lacks specificity-conferring residues. Insertion of such residues brings JunB under JNK control. JunD, by contrast, lacks a JNK docking site, but its phosphoacceptor peptide is identical to that of c-Jun. Substrates such as JunD can be phosphorylated by JNK through heterodimerization with docking competent partners. Therefore, heterodimerization can affect the recognition of transcription factors by signal-regulated protein kinases.
结构相关的丝氨酸/苏氨酸激酶在体外能识别相似的磷酸化受体肽，但在体内，它们磷酸化不同的底物。为了理解这种特异性的基础，我们研究了Jun激酶（JNKs）与Jun蛋白之间的相互作用。JNKs能非常高效地磷酸化c-Jun，对JunD的磷酸化效率较低，但它们不磷酸化JunB。有效的JNK底物需要一个单独的对接位点以及磷酸化受体两侧的特异性赋予残基。对接位点提高了磷酸化反应的效率和特异性。JunB有一个功能性的JNK对接位点，但缺乏特异性赋予残基。插入这些残基可使JunB受JNK控制。相比之下，JunD缺乏JNK对接位点，但其磷酸化受体肽与c-Jun的相同。像JunD这样的底物可通过与具有对接能力的伙伴异源二聚化而被JNK磷酸化。因此，异源二聚化可影响信号调节蛋白激酶对转录因子的识别。
