PubMed Journals: Cell
Source: PMID: 8221888
⇦ ⇨ Cell. 1993 Nov 5;75(3):487-93.
MKP-1 (3CH134), an immediate early gene
product, is a dual specificity phosphatase
that dephosphorylates MAP kinase in vivo.
Sun H(1), Charles CH, Lau LF, Tonks NK.
(1) Cold Spring Harbor Laboratory, New York
Mitogenic stimulation of cells induces rapid
and transient activation of MAP kinases.
Here we report that a growth factor-inducible
gene, 3CH134, encodes a dual specificity
phosphatase that dephosphorylates and inactivates
p42MAPK both in vitro and in vivo. In vitro,
3CH134 protein dephosphorylates both T183
and Y185 in p42MAPK. In serum-stimulated
normal fibroblasts, the kinetics of inactivation
of p42MAPK coincides with the appearance
of newly synthesized 3CH134 protein, and
the protein synthesis inhibitor cycloheximide
leads to persistent activation of MAP kinase.
Expression of 3CH134 in COS cells leads
to selective dephosphorylation of p42MAPK
from the spectrum of phosphotyrosyl proteins.
3CH134 blocks phosphorylation and activation
of p42MAPK mediated by serum, oncogenic
Ras, or activated Raf, whereas the catalytically
inactive mutant of the phosphatase, Cys-258-->Ser,
augments MAP kinase phosphorylation under
similar conditions. The mutant 3CH134 protein
also forms a physical complex with the
phosphorylated form of p42MAPK. These findings
suggest that 3CH134 is a physiological MAP
kinase phosphatase; we propose the name
MKP-1 for this phosphatase.
PMID: 8221888 [Indexed for MEDLINE]