nitrophenols and acetylleucyl-leucyl-norleucinal

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.

Topics: Animals; Blood; Cell Cycle Proteins; Cell Division; Cell Line; Cricetinae; Culture Media; Cysteine Endopeptidases; Cysteine Proteinase Inhibitors; Dual Specificity Phosphatase 1; Estradiol; Humans; Immediate-Early Proteins; Leucine; Leupeptins; MAP Kinase Signaling System; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Mitogen-Activated Protein Kinases; Multienzyme Complexes; Mutation; Nitrophenols; Organophosphorus Compounds; Phosphoprotein Phosphatases; Phosphorylation; Proteasome Endopeptidase Complex; Protein Phosphatase 1; Protein Tyrosine Phosphatases; Ubiquitins