Gary Wayman

Washington State University B.S.Biochemistry
University of Washingon Ph..D. Pharmacology
Assistant Professor, Cell and Developmental Biology

CaM Kinase IV is a multifunctional serine/threonine kinase, which is activated as part of a Ca2+/calmodulin dependent protein kinase cascade. Although the substrate specificity of CaM KIV is poorly established, it phosphorylates numerous transcription factors and is likely to have a physiological role in transcriptional regulation of calcium-dependent gene expression. While a role for CaM KIV in learning and memory has been postulated, the potential involvement of the CaM kinase cascade in embryonic patterning has not been established. Using the Xenopus embryo as a model system, we have shown that CaM KIV transcripts are widely distributed in the early embryo, and that strict regulation of CaM kinase activity during development is essential for hemotopoiesis. In Xenopus embryos, inhibition of CaM KIV activity causes commitment of hematopoietic precursors to myeloid differentiation at the expense of erythroid differentiation. Whereas constitutive activation of CaM KIV induces erythroid precursors to undergo apoptotic cell death. Blood defects are observed even when activity is misregulated solely in cells that do not contribute to the erythroid lineage. Thus, proper regulation of CaM KIV activity in non-hemotopoietic tissues is essential for the generation of extrinisic signals that enable hemotopoietic stem cell commitment to erythroid differentiation and that support the survival of erythroid precursors. The mechanism by which CaM KIV regulates hematopoisis is not completely understood. However, we have demonstrated that CaM KIV inhibits bone morphogenic protien (BMP) signaling during early development. BMPs are members of the TGF

Walters M. J., Wayman G. A., and Christian J. L., Bone Morphogentic Protein Function is Required for Terminal Differentiation, but not for Initial Specification, of the Heart, Mechanisms of Development (2001) Vol. 100 pp. 263-273.

Wayman G. A., Walters M. J., Kolibaba J., Soderling T. R., and Christian J. L., Calmodulin-Dependent Protein Kinase IV Functions Non cell Autonomously to Regulate Lineage Commitment and Survival of Erythroid Progenitors. Journal of Cell Biology (2000) Vol. 151 pp. 811-824.

Impey S., Obrietan K., Yano S., Wayman G. A., Wong S. T., Poser S., Deloume J. C., Chan G., Mark M., and Storm D R., Crosstalk Between ERK and PKA is Required For Ca2+ Stimulation of CREB-Deppendent Transcription and Nuclear Translocation Neuron (1998) Vol. 21 pp. 869-883.

Xia X. M., Fakler B., Rivard A.,. Wayman G. A., Johnson-Pais T., Keen j. E., Ishii T., Hirschber B., Bond C. T., Lutsenko S., and Adelman J. P., Mechanism of calcium gating in small conductance calcium-activated potassium channels Nature (1998) Vol. 395 pp. 503-507

Wayman G. A., Tokumitsu, H., and Soderling T. R., Inhibitory Cross-Talk by cAMP Kinase on the Calmodulin-Dependent Protein Kinase Cascade. Journal of Biological Chemistry (1997) Vol 272 No. 26 pp 16073-16076

Wayman G. A., Wei J., Wong S., and Storm D. R., Regulation of Type I Adenylyl Cyclase by CaM Kinase IV In Vivo. Molecular and Cellular Biology (1996) Vol 16 No 11 pp 6075-6082

Wei J., Wayman G. A., and Storm D. R., Phosphorylation and Inhibition of Type III Adenylyl Cyclase by Calmodulin-Dependent Protein Kinase II In Vivo Journal of Biological Chemistry (1996) Vol 271 No 39 pp 24231-24235

To contact Dr. Wayman directly: waymang@ohsu.edu