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PMID: 8013650 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't

Growth factor-stimulated MAP kinase induces rapid retrophosphorylation and inhibition of MAP kinase kinase (MEK1).

FEBS letters ·Vol. 346 ·No. 2-3 ·1994-06-13 ·Pages 299-303

Brunet A, Pagès G, Pouysségur J

Abstract

The MAP kinase module (Raf/MAPKKK-MAPKK-MAPK) has been shown to be sequentially activated after mitogenic stimulation. Here we demonstrate, by site directed mutagenesis, that MAPK is able to retrophosphorylate its own activator, MAPKK, on two threonine residues Thr-292 and Thr-386 in vitro, and that these sites are also phosphorylated in vivo. A comparison of the kinetics of serum-mediated activation of a wild-type MAPKK and of a mutant unable to undergo phosphorylation by MAPK suggests that this retrophosphorylation may be involved in a negative feedback control of the cascade in vivo.

MeSH Terms

Animals Binding Sites Cricetinae Cricetulus Enzyme Activation Feedback Growth Substances/pharmacology Immunosorbent Techniques Kinetics Mitogen-Activated Protein Kinase 1 Mitogen-Activated Protein Kinase Kinases Mutagenesis, Site-Directed Phosphorylation Phosphothreonine/metabolism Protein Kinase Inhibitors Protein Kinases/genetics,metabolism Protein Serine-Threonine Kinases/metabolism Protein-Tyrosine Kinases/metabolism Structure-Activity Relationship Threonine/genetics Transfection

Chemicals

Growth Substances Protein Kinase Inhibitors Phosphothreonine Threonine Protein Kinases Protein-Tyrosine Kinases Protein Serine-Threonine Kinases Mitogen-Activated Protein Kinase 1 Mitogen-Activated Protein Kinase Kinases

Authors & Affiliations

3 authors, click to expand affiliations / ORCID

Brunet A

Centre de Biochimie-CNRS, Université de Nice, France.

Pagès G

Pouysségur J

Article Info

Journal

FEBS letters

Abbr.

FEBS Lett

ISSN

0014-5793

DOI

10.1016/0014-5793(94)00475-7

Published

1994-06-13

Pages

299-303

Language

English

Region

England

NLM ID

0155157

Subset

External Links

PubMed source DOI: 10.1016/0014-5793(94)00475-7 View journal details

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Growth factor-stimulated MAP kinase induces rapid retrophosphorylation and inhibition of MAP kinase kinase (MEK1).

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