Aa. Tokmakov et al., INHIBITION OF MAPK PATHWAY BY A SYNTHETIC PEPTIDE CORRESPONDING TO THE ACTIVATION SEGMENT OF MAPK, Biochemical and biophysical research communications (Print), 252(1), 1998, pp. 214-219
Mitogen-activated protein kinase (MAPK) is activated by phosphorylatio
n within its activation segment. Upon phosphorylation, the activation
segment refolds to provide the active conformation of the enzyme. We r
eported previously that a phosphorylation-sensitive secondary structur
e could be formed in a 26-amino-acid long synthetic peptide correspond
ing to the activation segment of Xenopus MAPK termed IDA (Inter-DFG-AP
E) MAPK peptide (Tokmakov, A. A., ct al 1997, Biochem. Biophys. Res. C
ommun. 236, 243-247). Here, we show that unphosphorylated IDA MAPK pep
tide can inhibit in vitro both MAPK and MAPK kinase activities with th
e inhibition constants of 82 and 18 mu M, respectively. Phosphorylated
forms of the peptide were of little effect. IDA MAPK peptide did not
inhibit significantly the activity of some other protein kinases, incl
uding MAPK homologue p38 kinase, suggesting the specificity for MAPK a
nd MAPK kinase. Microinjection of unphosphorylated IDA MAPK peptide in
to immature Xenopus oocytes significantly suppressed progesterone-indu
ced oocyte maturation by inhibiting activation of both MAPK and matura
tion promoting factor. Similar inhibition of maturation was registered
upon oocyte treatment with another specific inhibitor of MAPK pathway
, PD098059. These results depict IDA MAPK peptide as a selective inhib
itor of the MAPK pathway that can be used for the investigations of MA
PK-mediated signaling: (C) 1998 Academic Press.