Selective suppression of stress-activated protein kinase pathway by protein phosphatase 2C in mammalian cells

• Published in: FEBS letters Vol. 437; no. 3; pp. 172 - 176
• Main Authors: Hanada, Masahito, Kobayashi, Takayasu, Ohnishi, Motoko, Ikeda, Shoko, Wang, Hong, Katsura, Koji, Yanagawa, Yuchio, Hiraga, Akira, Kanamaru, Ryunosuke, Tamura, Shinri
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 23.10.1998
• Subjects: Animals; Calcium-Calmodulin-Dependent Protein Kinases - antagonists & inhibitors; Calcium-Calmodulin-Dependent Protein Kinases - metabolism; COS Cells; MAP Kinase Kinase 1; MAP Kinase Kinase 3; MAP Kinase Kinase 6; MAP Kinase Kinase 7; Mitogen-Activated Protein Kinase Kinases; Mitogen-Activated Protein Kinases; p38 Mitogen-Activated Protein Kinases; Phosphoprotein Phosphatases - genetics; Phosphoprotein Phosphatases - metabolism; Phosphoprotein Phosphatases - physiology; Phosphorylation - drug effects; Point Mutation; Protein Kinase Inhibitors; Protein Kinases - metabolism; Protein Phosphatase 2; Protein Phosphatase 2C; Protein-Serine-Threonine Kinases - antagonists & inhibitors; Protein-Serine-Threonine Kinases - metabolism; Protein-Tyrosine Kinases - antagonists & inhibitors; Protein-Tyrosine Kinases - metabolism; Saccharomyces cerevisiae Proteins; Signal Transduction - drug effects; Signal Transduction - physiology; Stress-activated protein kinase signal pathway; Tyrosine - metabolism; Stress-activated protein kinase signal pathway; Protein phosphatase 2C
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/S0014-5793(98)01229-0

Protein phosphatase 2Cα (PP2Cα) or PP2Cβ-1 expressed in COS7 cells suppressed anisomycin- and NaCl-enhanced phosphorylations of p38 co-expressed in the cells. PP2Cα or PP2Cβ-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 PP2Cα or PP2Cβ-1 expression. However, basal as well as serum-activated phosphorylation of MKK1a, an upstream protein kinase of ERKs, was not affected by PP2Cβ or PP2Cβ-1. A catalytically inactive mutant of PP2Cβ-1 further enhanced the NaCl-stimulated phosphorylations of MMK3b, MKK4 and MKK6b, suggesting that this mutant PP2Cβ-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.