Signaling Pathways in the Control of Cell Architecture

Eukaryotic cells exert remarkable control over their three-dimensional organization. This control of morphogenesis is central to cell division, motility, and differentiation, and requires orchestration of diverse processes. My laboratory is interested in understanding how protein kinase signaling pathways coordinate cytoskeleton organization, membrane traffic, and gene expression to define cell architecture. We are using the budding yeast Saccharomyces cerevisiae to determine the exact physiological functions and relevant phosphorylation targets of highly conserved kinases that control important aspects of cell morphology.

Our present work is concentrated on understanding the functions of p21-activated kinases (PAKs) and the Ndr/warts family kinase Cbk1. The PAKs are important in early bud formation and establishment of the cytokinesis site, and may have undefined functions during late cell division. We are investigating PAK regulation of cytoskeletal proteins important for bud morphogenesis. Cbk1 is required throughout the cell cycle for sustained polarized growth, and may control localization of cell wall modifying machinery. Interestingly, Cbk1 also coordinates the transcription of genes required for mother/daughter separation with exit from mitosis. This function likely involves regulation of the nuclear export of Ace2, a highly conserved transcription factor.

Understanding how any protein kinase relays information requires identification of its regulatory partners and downstream phosphorylation targets. We are taking diverse approaches to this difficult problem. In addition to well-established genetic and biochemical techniques, we are using novel chemical genetic methods for in vivo and in vitro characterization of individual protein kinase functions and targets. This work involves both careful phenotypic analysis and proteome-scale investigation of potential phosphorylation targets.

Jansen, J.M., Barry, M.F., Yoo, C.K., and E. L. Weiss. Phosphoregulation of Cbk1 is critical for RAM network control of transcription and morphogenesis. Journal of Cell Biology, 2006 Dec 4;175(5):755-66.

Weiss, E. L., Kurischko, C., Zhang, C., Shokat, K., Drubin, D. G., and F. C. Luca. 2002. The S. cerevisiae Mob2p-Cbk1p kinase complex promotes polarized growth and acts with the Mitotic Exit Network to facilitate daughter cell-specific localization of Ace2p transcription factor. Journal of Cell Biology. 158(5):885-900.

Bidlingmaier, S., Weiss, E., Seidel, C., Drubin, D. G., and M. Snyder. 2001. The Cbk1p pathway is important for polarized cell growth and cell separation in Saccharomyces cerevisiae. Molecular and Cellular Biology, 21(7):2449-62.

Weiss, E., Bishop, A. C., Shokat, K. M., and D. G. Drubin. 2000. Chemical genetic analysis of the Saccharomyces cerevisiae p21-activated kinase Cla4p. Nature Cell Biology, 2(10):677-8.

View all publications by publications by Eric Weiss listed in the National Library of Medicine (PubMed).