Reduced MAP kinase phosphatase-1 degradation after p42/p44MAPK-dependent phosphorylation.
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.
Brondello
J M
JM
Institute of Signaling, Developmental Biology and Cancer Research, CNRS UMR 6543, Centre A. Lacassagne, 33 Avenue de Valombrose, Nice 06189, France.
Pouysségur
J
J
McKenzie
F R
FR
D000818:Animals; D001769:Blood; D018797:Cell Cycle Proteins; D002455:Cell Division; D002460:Cell Line; D006224:Cricetinae; D003470:Culture Media; D003546:Cysteine Endopeptidases / Q000378:metabolism; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D054638:Dual Specificity Phosphatase 1; D004958:Estradiol / Q000494:pharmacology; D006801:Humans; D017874:Immediate-Early Proteins / Q000737:chemistry / Q000378:metabolism*; D007930:Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D007976:Leupeptins / Q000494:pharmacology; D020935:MAP Kinase Signaling System; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009097:Multienzyme Complexes / Q000378:metabolism; D009154:Mutation; D009596:Nitrophenols / Q000378:metabolism; D009943:Organophosphorus Compounds / Q000378:metabolism; D010749:Phosphoprotein Phosphatases; D010766:Phosphorylation; D046988:Proteasome Endopeptidase Complex; D054645:Protein Phosphatase 1; D017027:Protein Tyrosine Phosphatases / Q000737:chemistry / Q000378:metabolism*; D014452:Ubiquitins / Q000378:metabolism
D018797:Cell Cycle Proteins; D003470:Culture Media; D015853:Cysteine Proteinase Inhibitors; D017874:Immediate-Early Proteins; D007976:Leupeptins; D009097:Multienzyme Complexes; D009596:Nitrophenols; D009943:Organophosphorus Compounds; D014452:Ubiquitins; C063261:acetylleucyl-leucyl-norleucinal; C008644:nitrophenylphosphate; D004958:Estradiol; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1; C517019:DUSP1 protein, human; D054638:Dual Specificity Phosphatase 1; D017027:Protein Tyrosine Phosphatases; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; D007930:Leucine; C024974:E 64