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Alan Wolfman, Ph.D.Associate Staff
Department of Cell Biology |
Area of general research interest:
Ras dependent signal transduction.
Current program:
- Signal transduction by specific Ras isoforms.
- Signaling systems that regulate myoblast differentiation.
- Signal tranduction by the naturally occuring activated Ras proteins.
Investigators:
- Liao, Jinhui, Ph.D.
- Patterson, Thomas, Ph.D.
- Planchon Pope, Sarah, Ph.D.
- Wolfman, Janice, Ph.D.
Collaborators:
- Willumsen, Berthe, Ph.D., Dept. Molecular Biology, University of Copenhagen, Denmark
- Kirschmeier, Paul, Ph.D., Schering Plough Research Institute, New Jersey
- Taparowsky, E.J. Ph.D., Dept. Biological Sceinces, Purdue University, Indiana.
Brief Description:
We are examining the signaling systems regulated by the specific Ras isoforms and their naturally occurring oncogenic proteins. We have set up systems in which naturally occurring activated Ras proteins are expressed at near endogenous levels. We are currently examining morphological and biochemical changes in cell lines either constitutively expressing these activating Ras proteins or by inducing their expression. Our goal is to understand (1) whether the different Ras isoforms signal through unique systems (2) whether the naturally occurring oncogenic Ras proteins signal through different mechanisms and (3) what are the minimum protein-protein interactions necessary for activated Ras proteins to elicit a transformed phenotype.
We are also examining the signaling systems which regulate myoblast differentiation into myotubes. The enigma in this system is that expression of activated Ras and the presence bFGF both inhibit myoblast differentiation. Stimulation with IGF-1, which also signals through Ras, however, results in an enhancement of myoblast differentiation. We are currently examining the signaling systems to determine the critical steps in the initiation and inhibition of myoblast differentiation.
Key References:
Cellular N-Ras promotes cell survival by down regulation of JNK and p38 (2002). Wolfman, J.C., Palmby, T., Der, C. and Wolfman, A. Mole. Cell Biol. 22, 1589-1606.
Ras isoform-specific signaling: Location, location, location (2001). Wolfman, A. Science's STKE 22(5), 1589-606. http://stke.sciencemag.org/cgi/content/full/OC_sigtrans;2001/96/pe2.
Endogenous c-N-Ras provides a steady-state anti-apoptotic signal. Wolfman, J.C. and Wolfman, A. (2000) JBC. 275, 19315-19323.
c-N-Ras, Raf-1 and PKCe are organized into latent signaling modules. Hamilton, H. Liao, J., Cathcart, M. and Wolfman, A. (2001). JBC 276, 29079-29090.
A direct interaction between oncogenic Ha-Ras and PI-3 kinase is not required for transformation. Karasarides, M., Anande-Apte, B. and Wolfman, A. (2001) J. Biol. Chem, 276, 39755-39764.