Cell Growth & Differentiation, Vol 4, Issue 5 377-385, Copyright © 1993 by American Association of Cancer Research

ARTICLES

Multiple signal transduction pathways mediate c-Jun protein phosphorylation

CC Franklin, T Unlap, V Adler and AS Kraft
Division of Hematology/Oncology, University of Alabama, Birmingham 35294.

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 found that c-Jun234 was expressed only in the cytosol and was inducibly phosphorylated with kinetics similar to those of endogenous nuclear c-Jun. Furthermore, we found that RasAsn17 had no effect on PMA-induced phosphorylation of c-Jun234. Because Ha-Ras requires isoprenylation for membrane binding, we examined the effect of the isoprenylation inhibitors lovastatin and perillic acid on PMA-induced c-Jun phosphorylation. Pretreatment of U937 cells with these agents had no effect on PMA-induced c-Jun or pp42 MAP kinase phosphorylation.(ABSTRACT TRUNCATED AT 250 WORDS)

This article has been cited by other articles:

				Y. H. Choi, M. J. Park, K. W. Kim, H. C. Lee, Y. H. Choi, and J. Cheong The orphan nuclear receptor SHP is involved in monocytic differentiation, and its expression is increased by c-Jun J. Leukoc. Biol., November 1, 2004; 76(5): 1082 - 1088. [Abstract] [Full Text] [PDF]

				H. He, X. Wang, M. Gorospe, N. J. Holbrook, and M. A. Trush Phorbol Ester-induced Mononuclear Cell Differentiation Is Blocked by the Mitogen-activated Protein Kinase Kinase (MEK) Inhibitor PD98059 Cell Growth Differ., May 1, 1999; 10(5): 307 - 315. [Abstract] [Full Text]

				C. Kitamura, K. Kimura, T. Nakayama, and M. Terashita Temporal and Spatial Expression of c-jun and jun-B Proto-oncogenes in Pulp Cells Involved with Reparative Dentinogenesis after Cavity Preparation of Rat Molars Journal of Dental Research, February 1, 1999; 78(2): 673 - 680. [Abstract] [PDF]

				M. Kaneki, S. Kharbanda, P. Pandey, K. Yoshida, M. Takekawa, J.-R. Liou, R. Stone, and D. Kufe Functional Role for Protein Kinase Cbeta as a Regulator of Stress-Activated Protein Kinase Activation and Monocytic Differentiation of Myeloid Leukemia Cells Mol. Cell. Biol., January 1, 1999; 19(1): 461 - 470. [Abstract] [Full Text] [PDF]

				C. C. Franklin, S. Srikanth, and A. S. Kraft Conditional expression of mitogen-activated protein kinase phosphatase-1, MKP-1, is cytoprotective against UV-induced apoptosis PNAS, March 17, 1998; 95(6): 3014 - 3019. [Abstract] [Full Text] [PDF]

				C. C. Franklin and A. S. Kraft Conditional Expression of the Mitogen-activated Protein Kinase (MAPK) Phosphatase MKP-1 Preferentially Inhibits p38 MAPK and Stress-activated Protein Kinase in U937 Cells J. Biol. Chem., July 4, 1997; 272(27): 16917 - 16923. [Abstract] [Full Text] [PDF]

				G. A. R. Doyle, R. A. Pierce, and W. C. Parks Transcriptional Induction of Collagenase-1 in Differentiated Monocyte-like (U937) Cells is Regulated by AP-1 and an Upstream C/EBP-beta Site J. Biol. Chem., May 2, 1997; 272(18): 11840 - 11849. [Abstract] [Full Text] [PDF]

				C. Kitamura and M. Terashita Expressions of c-jun and jun-B Proto-oncogenes in Odontoblasts during Development of Bovine Tooth Germs Journal of Dental Research, April 1, 1997; 76(4): 822 - 830. [Abstract] [PDF]