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PMID: 7504457 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Dual phosphorylation and autophosphorylation in mitogen-activated protein (MAP) kinase activation.

The Biochemical journal ·Vol. 296 ( Pt 1) ·1993-11-15 ·Pages 25-31

Her JH, Lakhani S, Zu K, Vila J, Dent P, Sturgill TW, Weber MJ

Abstract

p42mapk [mitogen activated protein (MAP) kinase; extracellular signal-regulated protein kinase (ERK)] is a serine/threonine-specific protein kinase that is activated by dual tyrosine and threonine phosphorylation in response to diverse agonists. Both the tyrosine and threonine phosphorylations are necessary for full enzymic activity. A MAP kinase activator recently purified and cloned has been shown to be a protein kinase (MAP kinase kinase) that is able to induce the dual phosphorylation of MAP kinase on both the regulatory tyrosine and threonine sites in vitro. In the present paper we have utilized MAP kinase mutants altered in the sites of regulatory phosphorylation to show, both in vivo and in vitro, that phosphorylation of the tyrosine and the threonine can occur independently of one another, with no required order of phosphorylation. We also utilized kinase-defective variants of MAP kinase with mutations in either the ATP-binding loop or the catalytic loop, and obtained data suggesting that the activity or structure of the catalytic loop of MAP kinase plays an important role in its own dual phosphorylation.

MeSH Terms
Amino Acid Sequence Amino Acids/analysis Animals Antibodies, Monoclonal Base Sequence Calcium-Calmodulin-Dependent Protein Kinases/biosynthesis,metabolism Enzyme Activation Epitopes/analysis,biosynthesis Kinetics Mitogen-Activated Protein Kinase Kinases Molecular Sequence Data Muscles/enzymology Mutagenesis, Site-Directed Oligodeoxyribonucleotides Peptides/chemical synthesis,immunology Phosphates/metabolism Phosphorus Radioisotopes Phosphorylation Protein Kinases/metabolism Rabbits Recombinant Proteins/biosynthesis,metabolism
Chemicals
Amino Acids Antibodies, Monoclonal Epitopes Oligodeoxyribonucleotides Peptides Phosphates Phosphorus Radioisotopes Recombinant Proteins Protein Kinases Calcium-Calmodulin-Dependent Protein Kinases Mitogen-Activated Protein Kinase Kinases
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Her J H
Department of Microbiology, University of Virginia, Charlottesville 22908.
Lakhani S
Zu K
Vila J
Dent P
Sturgill T W
Weber M J
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41 references, click to expand
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Article Info
Journal
The Biochemical journal
Abbr.
Biochem J
ISSN
0264-6021
DOI
10.1042/bj2960025
Published
1993-11-15
Pages
25-31
Language
English
Region
England
NLM ID
2984726R
PMCID
PMC1137650
Subset
IM
Grants
NCI NIH HHS · CA39076 · United States
NCI NIH HHS · CA40042 · United States
NIGMS NIH HHS · GM47332 · United States
External Links
PubMed source DOI: 10.1042/bj2960025 PMC Full Text View journal details
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