Camps M, Nichols A, Gillieron C, Antonsson B, Muda M, Chabert C, Boschert U, Arkinstall S
Geneva Biomedical Research Institute, Glaxo Wellcome Research and Development S.A., CH-1228 Plan-les-Ouates, Geneva, Switzerland.
Science. 1998 May 22;280(5367):1262-5. doi: 10.1126/science.280.5367.1262.
MAP kinase phosphatase-3 (MKP-3) dephosphorylates phosphotyrosine and phosphothreonine and inactivates selectively ERK family mitogen-activated protein (MAP) kinases. MKP-3 was activated by direct binding to purified ERK2. Activation was independent of protein kinase activity and required binding of ERK2 to the noncatalytic amino-terminus of MKP-3. Neither the gain-of-function Sevenmaker ERK2 mutant D319N nor c-Jun amino-terminal kinase-stress-activated protein kinase (JNK/SAPK) or p38 MAP kinases bound MKP-3 or caused its catalytic activation. These kinases were also resistant to enzymatic inactivation by MKP-3. Another homologous but nonselective phosphatase, MKP-4, bound and was activated by ERK2, JNK/SAPK, and p38 MAP kinases. Catalytic activation of MAP kinase phosphatases through substrate binding may regulate MAP kinase activation by a large number of receptor systems.
丝裂原活化蛋白激酶磷酸酶-3（MKP-3）可使磷酸酪氨酸和磷酸苏氨酸去磷酸化，并选择性地使细胞外信号调节激酶（ERK）家族的丝裂原活化蛋白（MAP）激酶失活。MKP-3通过与纯化的ERK2直接结合而被激活。这种激活不依赖于蛋白激酶活性，且需要ERK2与MKP-3的非催化性氨基末端结合。功能获得性ERK2突变体Sevenmaker D319N以及c-Jun氨基末端激酶-应激激活蛋白激酶（JNK/SAPK）或p38 MAP激酶均不与MKP-3结合，也不会导致其催化激活。这些激酶对MKP-3的酶促失活也具有抗性。另一种同源但非选择性的磷酸酶MKP-4可与ERK2、JNK/SAPK和p38 MAP激酶结合并被其激活。通过底物结合实现的MAP激酶磷酸酶的催化激活可能由大量受体系统调节MAP激酶的激活。
