Tanoue T, Adachi M, Moriguchi T, Nishida E
Department of Biophysics, Graduate School of Science, Kyoto University, Sakyo-ku, Kyoto 606-8502, Japan.
Nat Cell Biol. 2000 Feb;2(2):110-6. doi: 10.1038/35000065.
Mitogen-activated protein kinases (MAPKs) are specifically phosphorylated and activated by the MAPK kinases, phosphorylate various targets such as MAPK-activated protein kinases and transcription factors, and are inactivated by specific phosphatases. Recently, docking interactions via the non-catalytic regions of MAPKs have been suggested to be important in regulating these reactions. Here we identify docking sites in MAPKs and in MAPK-interacting enzymes. A docking domain in extracellular-signal-regulated kinase (ERK), a MAPK, serves as a common site for binding to the MAPK kinase MEK1, the MAPK-activated protein kinase MNK1 and the MAPK phosphatase MKP3. Two aspartic acids in this domain are essential for docking, one of which is mutated in the sevenmaker mutant of Drosophila ERK/Rolled. A corresponding domain in the MAPKs p38 and JNK/SAPK also serves as a common docking site for their MEKs, MAPK-activated protein kinases and MKPs. These docking interactions increase the efficiency of the enzymatic reactions. These findings reveal a hitherto unidentified docking motif in MAPKs that is used in common for recognition of their activators, substrates and regulators.
丝裂原活化蛋白激酶（MAPKs）由丝裂原活化蛋白激酶激酶特异性磷酸化并激活，可磷酸化多种靶点，如丝裂原活化蛋白激酶激活的蛋白激酶和转录因子，并被特定的磷酸酶灭活。最近，有人提出通过丝裂原活化蛋白激酶的非催化区域进行对接相互作用在调节这些反应中很重要。在这里，我们确定了丝裂原活化蛋白激酶和与丝裂原活化蛋白激酶相互作用的酶中的对接位点。丝裂原活化蛋白激酶之一的细胞外信号调节激酶（ERK）中的一个对接结构域，作为与丝裂原活化蛋白激酶激酶MEK1、丝裂原活化蛋白激酶激活的蛋白激酶MNK1和丝裂原活化蛋白激酶磷酸酶MKP3结合的共同位点。该结构域中的两个天冬氨酸对于对接至关重要，其中一个在果蝇ERK/Rolled的sevenmaker突变体中发生了突变。丝裂原活化蛋白激酶p38和JNK/SAPK中的相应结构域也作为它们的丝裂原活化蛋白激酶激酶、丝裂原活化蛋白激酶激活的蛋白激酶和丝裂原活化蛋白激酶磷酸酶的共同对接位点。这些对接相互作用提高了酶促反应的效率。这些发现揭示了丝裂原活化蛋白激酶中一个迄今未被识别的对接基序，该基序被共同用于识别它们的激活剂、底物和调节剂。
