Activation of c-Jun-NH2-Kinase by UV Irradiation Is Dependent on p21

We have recently found that the p21ras protein stimulates phosphorylation of JNK and enhances JNK-catalyzed phosphorylation of c-Jun

Victor Adler; Matthew R. Pincus; Alla Polotskaya; Ximena Montano; Fred K. Friedman; Ze'ev Ronai


Scholarcy highlights

  • Jun-NH2-kinase1 represents a family of stress-activated protein kinases that phosphorylate serine/threonine in the NH2-terminal domain of transcription factors c-Jun, ATF2, ELK1, and p53
  • Protein kinase pathway results in the activation of transcription factors other than those activated by the MEKK and JNKK pathway, certain cross-talk between the two pathways appears to exist
  • Control reactions in which the same membranes were incubated with antibodies to p21ras revealed equal amounts of p21ras in the precipitable complex before and after UV irradiation
  • Control reactions were performed by incubating these cells with different peptides, including epidermal growth factor receptor, Src, mitogen-activated protein kinase, and a mutant form of the Ras peptide corresponding to amino acids 96 –110
  • That the amount of p21ras-bound JNK depends on cellular stress and increases significantly after UV irradiation points to a role for p21ras in UV-mediated JNK activation
  • For non-dexamethasone-treated M1311 cells, a significant reduction in the degree of JNK activation was observed
  • Recent studies suggest that JNK binds to growth factor receptor binding protein 2, the adapter protein that links tyrosine kinase receptors to the SOS protein, which, in turn, activates p21ras by promoting GTP/GDP exchange. These findings suggest that JNK may be activated in the cytosol near the cell membrane, different JNK isozymes may be activated by alternate pathways, which include nuclear DNA lesions formed after UV irradiation
  • Because other kinases were shown capable of phosphorylating ATF2, which forms a heterodimer with c-Jun for binding to the UV response element , we cannot exclude the possibility that the mechanism of inhibition of URE-DNA binding activity, Ras-dependent, is not solely related to JNK

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