Reduced MAP kinase phosphatase-1 degradation after p42/p44(MAPK)-dependentphosphorylation

The mitogen-activated protein (MAP) kinase cascade is inactivated at the le vel of MAP kinase by members of the MAP kinase phosphatase (MKP) family, in cluding MKP-1. MKP-1 was a labile protein in CCL39 hamster fibroblasts; its degradation was attenuated by inhibitors of the ubiquitin-directed proteas ome complex; MKP-1 was a target in vivo and in vitro for p42(MAPK) or p44(M APK), which phosphorylates MKP-1 on two carboxyl-terminal serine residues, Serine 359 and Serine 364. This phosphorylation did not modify MKP-1's intr insic ability to dephosphorylate p44(MAPK) but led to stabilization of the protein. These results illustrate the importance of regulated protein degra dation in the control of mitogenic signaling.