Reduced MAP Kinase Phosphatase-1 Degradation After p42/p44 MAPK -Dependent Phosphorylation

Abstract

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.