M. Hanada et al., SELECTIVE SUPPRESSION OF STRESS-ACTIVATED PROTEIN-KINASE PATHWAY BY PROTEIN PHOSPHATASE 2C IN MAMMALIAN-CELLS, FEBS letters, 437(3), 1998, pp. 172-176
Protein phosphatase 2C alpha (PP2C alpha) or PP2C beta-1 expressed in
COS7 cells suppressed anisomycin- and NaCl-enhanced phosphorylations o
f p38 co-expressed in the cells. PP2C alpha or PP2C beta-1 expression
also suppressed both basal and stress-enhanced phosphorylations of MKK
3b and MKK6b, which are upstream protein kinases of p38, and of MKK4,
which is one of the major upstream protein kinases of JNK. Basal activ
ity of MKK7, another upstream protein kinase of JNK, was also suppress
ed by PP2C alpha or PP2C beta-1 expression. However, basal as well as
serum-activated phosphorylation of MKK1a, an upstream protein kinase o
f ERKs, was not affected by PP2C beta or PP2C beta-1. A catalytically
inactive mutant of PP2C beta-1 further enhanced the NaCl-stimulated ph
osphorylations of MMK3b, MKK4 and MKK6b, suggesting that this mutant P
P2C beta-1 works as a dominant negative form. These results suggest th
at PP2C selectively inhibits the SAPK pathways through suppression of
MKK3b, MKK4, MKK6b and MKK7 activities in mammalian cells. (C) 1998 Fe
deration of European Biochemical Societies.