Reduced MAP kinase phosphatase-1 degradation after p42/p44MAPK-dependent phosphorylation
Reduced MAP kinase phosphatase-1 degradation after p42/p44MAPK-dependent phosphorylation
复制标题
DOI：
10.1126/science.286.5449.2514
复制
发表时间：
1999-12-24
期刊：
影响因子：
56.9
通讯作者：
McKenzie, FR
中科院分区：
文献类型：
--
作者：
Brondello, JM;Pouysségur, J;McKenzie, FR
丝裂原活化蛋白(MAP)激酶级联在MAP激酶水平上被MKP家族成员失活，包括MKP-1。MKP-1在CCL39金黄地鼠成纤维细胞中是一种不稳定的蛋白质；它的降解被泛素导向的蛋白酶体复合体抑制剂减弱；MKP-1在体内和体外是p42(MAPK)或p44(MAPK)的靶标，它使MKP-1在两个羧基末端的丝氨酸残基，丝氨酸359和丝氨酸364上磷酸化。这种磷酸化并没有改变MKP-1‘S对p44(MAPK)的去磷酸化能力，但导致了该蛋白的稳定。这些结果说明了调节蛋白质降解在控制有丝分裂信号中的重要性。
The mitogen-activated protein (MAP) kinase cascade is inactivated at the level of MAP kinase by members of the MAP kinase phosphatase (MKP) family, including MKP-1. MKP-1 was a labile protein in CCL39 hamster fibroblasts; its degradation was attenuated by inhibitors of the ubiquitin-directed proteasome complex; MKP-1 was a target in vivo and in vitro for p42(MAPK) or p44(MAPK), which phosphorylates MKP-1 on two carboxyl-terminal serine residues, Serine 359 and Serine 364. This phosphorylation did not modify MKP-1's intrinsic ability to dephosphorylate p44(MAPK) but led to stabilization of the protein. These results illustrate the importance of regulated protein degradation in the control of mitogenic signaling.