Regulation of A Kinase Cascade Involved in Cancer and Normal Cell Growth

摘要

This award was used to train Dr. Minhong Yan during his Ph.D. research, and as such has been highly successful. Dr. Yan received his Ph.D. in May of 1997, and began a Post-Doctoral fellowship in July 1 1997. In experiments performed under this award, Dr. Yan first mapped sites of phosphorylation on the MEK1 protein kinase, and next identified the role of the MEKK1 protein kinase in signal transduction, placing it upstream of the SEK1 kinase and the Stress- Activated Protein Kinase. MEKK1 directly phosphorylates tSEK1, which in turn phosphorylates SAPK. Subsequent to accomplishment of this Aim, Dr. Yan has identified a novel activity of MEKK1, specifically a tyrosine kinase activity associated with the MEKK1 kinase (thought to be exclusively a serine/threonine kinase heretofore) as well as a cellular substrate of MEKK that becomes phosphorylated on tyrosine to undetermined ends.