Complexes of p21RAS with JUN N-terminal kinase and JUN proteins (original) (raw)
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Annals of clinical and laboratory science, 2008
In a study of interactions between the raf-MEK-MAPK (ERK) and JNK-jun pathways, we found previously that JNK can induce phosphorylation of raf but not vice versa. In this study, we investigate the nature of the JNK-induced phosphorylation of raf. In in vitro experiments in which immunobead-bound raf is phosphorylated by activated JNK, we find strong phosphorylation signals at raf-Ser259 and Ser338. The Ser259 phosphorylation is surprising since it is associated with inhibition of migration of raf to the cell membrane where it can interact with ras-p21. We also find that in oocytes induced to mature with oncogenic ras-p21, which induces high levels of phosphorylated JNK and MAPK, the same pattern of phosphorylation of raf occurs. In contrast, in oocytes induced to mature with insulin, which requires activation of wild-type ras-p21, phosphorylation of raf-Ser338 but not raf-Ser259 occurs. In oncogenic ras-transformed human pancreatic cancer MIA-PaCa-2 cells, phosphorylation of both ra...
Activation of c-Jun-NH2-kinase by UV irradiation is dependent on p21ras
1996
We have demonstrated previously that Jun-NH 2-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.
Activation of c-Jun-NH2-Kinase by UV Irradiation Is Dependent on p21
Journal of Biological Chemistry, 1996
We have demonstrated previously that Jun-NH 2-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.
jun-B inhibits and c-fos stimulates the transforming and trans-activating activities of c-jun
Cell, 1989
We have cloned the human jun-6 gene and determined its sequence and transforming and trans-activating activities. jun-6 is less potent than c-jun in transforming and immortalizing primary rat embryo cells in cooperation with activated ras (effects enhanced by c-fos and TPA); unlike c-jun, jun43 does not transform RaMA cells alone. However, cotransfection of c-jun and jun-8 into primary rat embryo cells with c-Ha-ras results in a signlflcant decrease In transformation compared with c-jun alone, an event reversed by TPA. Cotransfection of c-jun and jun-l with or without c-fos into F9 teratocarcinoma cells results in decreased frans-activation of APl compared with either gene alone. introduction of jun-B into primary rat c-junlras transformants or c-jun into jun-Blras transformants also results in a decrease in trans-activation. These findings demonstrate that, whereas jmb and c-jun each participate in APl tfans-activation and mallgnant transformation, interactions between them involve negative regulation.
Multiple signal transduction pathways mediate c-Jun protein phosphorylation
Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research, 1993
A variety of protein kinases, including pp42 and pp54 mitogen-activated protein (MAP) kinases, p34cdc2, and a partially purified protein kinase from 4 beta-phorbol 12-myristate 13 alpha-acetate (PMA)-treated U937 cells have been shown to phosphorylate the NH2-terminal activation domain of c-Jun in vitro. To investigate the role of pp42 MAP kinase in mediating c-Jun phosphorylation in vivo, we have treated U937 monocytic leukemia cells with a variety of pharmacological agents, including PMA, cycloheximide, AIF4, and okadaic acid. Although all of these agents stimulated c-Jun phosphorylation, cycloheximide and okadaic acid had no effect on pp42 MAP kinase phosphorylation, suggesting that MAP kinase activation was not necessary for c-Jun phosphorylation in vivo. Because dominant-negative RasAsn17 has been shown to block the effects of PMA on pp42 MAP kinase phosphorylation, we assessed its effect on c-Jun phosphorylation by cotransfection with a truncated c-Jun construct (c-Jun234). We...