Activation of c-Jun-NH2-kinase by UV irradiation is dependent on p21ras.
We have demonstrated previously that Jun-NH2-kinase (JNK) activation in vitro is potentiated by association with the p21(ras) protein. To determine if in vivo activation of JNK also depends on p21(ras), we have used M1311 cells that carry the cDNA for the neutralizing antibody to p21(ras), Y13-259, under a dexamethasone-inducible promoter. The ability of UV to activate JNK gradually decreased over a 4-day period of cell growth in dexamethasone. This decrease coincides with weaker transcriptional activation measured via gel shift and chloramphenicol acetyltransferase assays. Peptides corresponding to amino acids 96-110 on p21(ras), which were shown to block Ras-JNK association, inhibited UV-mediated JNK activation in mouse fibroblast 3T3-4A cells as well as in M1311 cells, further supporting the role of p21(ras) in UV-mediated JNK activation. Overall, the present studies provide in vivo confirmation of the role p21(ras) plays in JNK activation by UV irradiation.
Adler
V
V
Molecular Carcinogenesis Program, American Health Foundation, Valhalla, New York 10595, USA.
Pincus
M R
MR
Polotskaya
A
A
Montano
X
X
Friedman
F K
FK
Ronai
Z
Z
D016475:3T3 Cells; D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism* / Q000528:radiation effects*; D004789:Enzyme Activation / Q000528:radiation effects; D005786:Gene Expression Regulation; D048031:JNK Mitogen-Activated Protein Kinases; D051379:Mice; D020928:Mitogen-Activated Protein Kinases; D009500:Neutralization Tests; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000378:metabolism*; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection; D014466:Ultraviolet Rays
D016755:Proto-Oncogene Proteins c-jun; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D016283:Proto-Oncogene Proteins p21(ras)