Phil Stork

Scientist, Vollum Institute
Associate Professor, Cell and Developmental Biology

The Stork laboratory has been interested in the mechanism of hormonal and growth factor regulation of cell proliferation. Much work have centered on the Mitogen-activated protein (MAP) kinase cascade which direct signals to proliferation and differentiation in all cell types. The laboratory has identified a novel signaling pathway utilized by growth factors and hormones provides cell type specific control signals to MAP kinase cascades. A focus of the lab's attention over the past few years has been the G proteins Ras and Rap1, a member of the Ras super-family. Rap1 can both activate signals to the MAP kinase cascade as well as inhibit signals to the MAP kinase cascade. This specificity is achieved via the expression of a Rap1 effector protein, B-Raf. In cells that do not express B-Raf, Rap1 inhibits Ras signaling via its sequestration of Raf-1. This cell type specificity provides added levels of regulation to multiple signaling pathways including those triggered by nerve growth factor, T cell receptor, and cAMP. The laboratory has developed assays to determine the mechanism of activation of Rap1 by these agents and utilize a number of physiological models to examine the role of these small G proteins in cell growth and differentiation.

Grewal, S. S., Fass, D. M., Yao, H., Ellig, C. L., Goodman, R. H. & Stork, P. J. S. (2001) J. Biol Chem.

Calcium and cAMP signals differentially regulate cAMP-responsive element-binding protein function via a Rap1-extracellular signal- regulated kinase pathway. 275, 34433-41.

Schmitt, J. M. & Stork, P. J. S. (2001) Mol. Cell Biol. Cyclic AMP-mediated inhibition of cell growth requires the small G protein rap1. 21, 3671-3683.

Carey, K. D., Dillon, T. J., Schmitt, J. M., Baird, A. M., Holdorf, A. D., Straus, D. B., Shaw, A. S. & Stork, P. J. S. (2000) CD28 and the tyrosine kinase lck stimulate mitogen-activated protein kinase activity in T cells via inhibition of the small G protein rap1. 22, 8409-19.

To contact Dr. Stork directly: stork@ohsu.edu