Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2003 Mar 15;370(Pt 3):1077-85.
doi: 10.1042/BJ20021806.

Docking sites on mitogen-activated protein kinase (MAPK) kinases, MAPK phosphatases and the Elk-1 transcription factor compete for MAPK binding and are crucial for enzymic activity

A Jane Bardwell  1 , Mahsa Abdollahi, Lee Bardwell
Affiliations

Docking sites on mitogen-activated protein kinase (MAPK) kinases, MAPK phosphatases and the Elk-1 transcription factor compete for MAPK binding and are crucial for enzymic activity

A Jane Bardwell et al. Biochem J. .

Abstract

Mitogen-activated protein kinase (MAPK) cascades control gene expression patterns in response to extracellular stimuli. MAPK/ERK (extracellular-signal-regulated kinase) kinases (MEKs) activate MAPKs by phosphorylating them; activated MAPKs, in turn, phosphorylate target transcription factors, and are deactivated by phosphatases. One mechanism for maintaining signal specificity and efficiency is the interaction of MAPKs with their substrates and regulators through high-affinity docking sites. In the present study, we show that peptides corresponding to the MAPK-docking sites of MEK1, MEK2, Ste7, Elk-1 and MAPK phosphatase (MKP)-2 potently inhibit MEK2 phosphorylation of ERK2, ERK2 phosphorylation of Elk-1, and MKP-1 dephosphorylation of ERK2. Each peptide inhibited multiple reactions; for example, the MEK2 peptide inhibited not only MEK2, but also ERK2 and MKP-1. In addition, these docking-site peptides inhibited MEK2-ERK2 binding. The MAPK-docking site of MEK1 also potently stimulated ERK2-mediated phosphorylation of a target site on the same peptide. Control peptides with mutations of conserved basic and hydrophobic residues of the MAPK-docking site consensus lacked biological activity. We conclude that MEKs, MKPs and the Elk-1 transcription factor compete for binding to the same region of ERK2 via protein-protein interactions that are crucial for kinase/phosphatase activity.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Mol Cell Biol. 1996 Nov;16(11):6486-93 - PubMed
    1. J Biol Chem. 1999 Oct 22;274(43):30349-52 - PubMed
    1. J Biol Chem. 2001 Jul 13;276(28):26509-15 - PubMed
    1. J Biol Chem. 2001 Jul 20;276(29):27256-65 - PubMed
    1. J Biol Chem. 2001 Jul 27;276(30):27770-7 - PubMed

Publication types

MeSH terms