Selective suppression of stress-activated protein kinase pathway by protein phosphatase 2C in mammalian cells.
Protein phosphatase 2Calpha (PP2Calpha) or PP2Cbeta-1 expressed in COS7 cells suppressed anisomycin- and NaCl-enhanced phosphorylations of p38 co-expressed in the cells. PP2Calpha or PP2Cbeta-1 expression also suppressed both basal and stress-enhanced phosphorylations of MKK3b and MKK6b, which are upstream protein kinases of p38, and of MKK4, which is one of the major upstream protein kinases of JNK. Basal activity of MKK7, another upstream protein kinase of JNK, was also suppressed by PP2Calpha or PP2Cbeta-1 expression. However, basal as well as serum-activated phosphorylation of MKK1alpha, an upstream protein kinase of ERKs, was not affected by PP2Cbeta or PP2Cbeta-1. A catalytically inactive mutant of PP2Cbeta-1 further enhanced the NaCl-stimulated phosphorylations of MMK3b, MKK4 and MKK6b, suggesting that this mutant PP2Cbeta-1 works as a dominant negative form. These results suggest that PP2C selectively inhibits the SAPK pathways through suppression of MKK3b, MKK4, MKK6b and MKK7 activities in mammalian cells.
Hanada
M
M
Department of Biochemistry, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.
Kobayashi
T
T
Ohnishi
M
M
Ikeda
S
S
Wang
H
H
Katsura
K
K
Yanagawa
Y
Y
Hiraga
A
A
Kanamaru
R
R
Tamura
S
S
D000818:Animals; D019556:COS Cells; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D048369:MAP Kinase Kinase 1; D048371:MAP Kinase Kinase 3; D048669:MAP Kinase Kinase 6; D048688:MAP Kinase Kinase 7; D020929:Mitogen-Activated Protein Kinase Kinases; D020928:Mitogen-Activated Protein Kinases; D010749:Phosphoprotein Phosphatases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D010766:Phosphorylation / Q000187:drug effects; D017354:Point Mutation; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000378:metabolism; D054648:Protein Phosphatase 2; D000071636:Protein Phosphatase 2C; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D014443:Tyrosine / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases
D047428:Protein Kinase Inhibitors; D029701:Saccharomyces cerevisiae Proteins; D014443:Tyrosine; D011494:Protein Kinases; D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D048369:MAP Kinase Kinase 1; D048371:MAP Kinase Kinase 3; D048669:MAP Kinase Kinase 6; D048688:MAP Kinase Kinase 7; D020929:Mitogen-Activated Protein Kinase Kinases; C087358:PTC1 protein, S cerevisiae; D010749:Phosphoprotein Phosphatases; D054648:Protein Phosphatase 2; D000071636:Protein Phosphatase 2C