Abstract
The ultraviolet (UV) response of mammalian cells is characterized by a rapid and selective increase in gene expression mediated by AP-1 and NF-kappa B. The effect on AP-1 transcriptional activity results, in part, from enhanced phosphorylation of the c-Jun NH2-terminal activation domain. Here, we describe the molecular cloning and characterization of JNK1, a distant relative of the MAP kinase group that is activated by dual phosphorylation at Thr and Tyr during the UV response. Significantly, Ha-Ras partially activates JNK1 and potentiates the activation caused by UV. JNK1 binds to the c-Jun transactivation domain and phosphorylates it on Ser-63 and Ser-73. Thus, JNK1 is a component of a novel signal transduction pathway that is activated by oncoproteins and UV irradiation. These properties indicate that JNK1 activation may play an important role in tumor promotion.
Publication types
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, Non-P.H.S.
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Amino Acid Sequence
-
Base Sequence
-
Binding Sites
-
Calcium-Calmodulin-Dependent Protein Kinases / chemistry
-
Cell Line
-
Enzyme Activation
-
Humans
-
JNK Mitogen-Activated Protein Kinases
-
Mitogen-Activated Protein Kinases*
-
Molecular Sequence Data
-
Oncogene Protein p21(ras) / physiology
-
Phosphorylation
-
Protein Binding
-
Protein Serine-Threonine Kinases / genetics
-
Protein Serine-Threonine Kinases / metabolism*
-
Protein Serine-Threonine Kinases / radiation effects
-
Proto-Oncogene Proteins c-jun / metabolism*
-
Sequence Homology, Amino Acid
-
Substrate Specificity
-
Transcriptional Activation
-
Ultraviolet Rays
Substances
-
Proto-Oncogene Proteins c-jun
-
Protein Serine-Threonine Kinases
-
Calcium-Calmodulin-Dependent Protein Kinases
-
JNK Mitogen-Activated Protein Kinases
-
Mitogen-Activated Protein Kinases
-
Oncogene Protein p21(ras)