Identification of an oncoprotein- and UV-responsive protein kinase that binds and potentiates the c-Jun activation domain

M Hibi; A Lin; T Smeal; A Minden; M Karin

doi:10.1101/gad.7.11.2135

Identification of an oncoprotein- and UV-responsive protein kinase that binds and potentiates the c-Jun activation domain

Genes Dev. 1993 Nov;7(11):2135-48. doi: 10.1101/gad.7.11.2135.

Authors

M Hibi¹, A Lin, T Smeal, A Minden, M Karin

Affiliation

¹ Department of Pharmacology, University of California San Diego, School of Medicine, La Jolla 92093-0636.

PMID: 8224842
DOI: 10.1101/gad.7.11.2135

Abstract

The activity of c-Jun is regulated by phosphorylation. Various stimuli including transforming oncogenes and UV light, induce phosphorylation of serines 63 and 73 in the amino-terminal activation domain of c-Jun and thereby potentiate its trans-activation function. We identified a serine/threonine kinase whose activity is stimulated by the same signals that stimulate the amino-terminal phosphorylation of c-Jun. This novel c-Jun amino-terminal kinase (JNK), whose major form is 46 kD, binds to a specific region within the c-Jun trans-activation domain and phosphorylates serines 63 and 73. Phosphorylation results in dissociation of the c-Jun-JNK complex. Mutations that disrupt the kinase-binding site attenuate the response of c-Jun to Ha-Ras and UV. Therefore the binding of JNK to c-Jun is of regulatory importance and suggests a mechanism through which protein kinase cascades can specifically modulate the activity of distinct nuclear targets.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

3T3 Cells
Amino Acid Sequence
Animals
Base Sequence
Binding Sites
Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
Cell Line
Cell Line, Transformed
Genes, ras
Glutathione Transferase / biosynthesis
Glutathione Transferase / metabolism
HeLa Cells
Humans
JNK Mitogen-Activated Protein Kinases
Mice
Mitogen-Activated Protein Kinases*
Molecular Weight
Mutagenesis, Site-Directed
Phosphorylation
Protein Serine-Threonine Kinases / metabolism*
Protein Serine-Threonine Kinases / radiation effects
Proto-Oncogene Proteins c-jun / biosynthesis
Proto-Oncogene Proteins c-jun / metabolism*
Recombinant Fusion Proteins / biosynthesis
Recombinant Fusion Proteins / metabolism
Serine
Transfection
Ultraviolet Rays*

Substances

Proto-Oncogene Proteins c-jun
Recombinant Fusion Proteins
Serine
Glutathione Transferase
Protein Serine-Threonine Kinases
Calcium-Calmodulin-Dependent Protein Kinases
JNK Mitogen-Activated Protein Kinases
Mitogen-Activated Protein Kinases