September 2005 Meeting Announcement, Delaware Valley Mass Spectrometry Discussion Group
- Topic: "Mass Spectrometry-based Tools for Understanding
Complex Patterns of Protein Phosphorylation
- Speaker: Roland S. Annan, GlaxoSmithKline Pharmaceuticals, King of Prussia PA
- Date: Monday, September 19, 2005. 6:30 PM
- Time: Social Hour: 6:30 PM.
Talk: 7:30 PM.
- Place: Fox Chase Cancer Center, Reimann Auditorium. 333 Cottman Avenue, Philadelphia,
- Directions:Park in the North parking lots along the North Drive (please see the Campus map at http://www.fccc.edu/information/campus_map.html) and enter the Reimann Building at its front entrance beside the circle. Once inside, you will be directed to the appropriate venue.
For directions and additional maps see http://www.fccc.edu/information/directions.html
Many intracellular signalling pathways are controlled by phosphorylation dependent activation of individual protein components of the pathway. Multiple phosphorylation sites on individual proteins appear to be quite common, and may be more the rule than the exception. While identifying multiple phosphorylation sites on individual proteins is now fairly reliable, understanding which phosphorylation sites modulate protein function or are active in a given biological pathway is still a difficult problem. Adding to the complexity of this problem is the fact that phosphorylation-dependent function may not depend on activity at a single site, but rather be dependent upon activation of several sites. In order to unravel phosphorylation dependent structure-function relationships, a thorough quantitative analysis of the phosphorylation profile of a protein is useful.
This talk describes how we have been developing and using mass spectrometry-based tools to provide a qualitative and quantitative view of how protein phosphorylation controls cellular processes. Recently we adapted a new hybrid triple quadrupole-linear ion trap mass spectrometer to be used in this work. This instrument operates with exquisite selectivity in the triple quadrupole MS mode and performs high sensitivity peptide sequencing while in the linear ion trap MS mode. This combination has allowed us to identify and monitor the activation of specific phosphorylation sites on individual proteins or in highly complex mixtures. With or without stable isotope tagging we are able to define subsets of in vivo activated phosphorylation sites which are functionally significant in a given pathway. Following this multiple, specific epitopes can be accurately monitored in a highly sensitive assay using mass spectrometry.
Dr. Roland Annan is an Associate Director in the Department of Computational Analytical and Structural Sciences at GlaxoSmithKline Pharmaceuticals. He is also Head of the Proteomics and Biological Mass Spectrometry Group in King of Prussia, PA. This group develops and applies mass spectrometry based solutions to problems in biology. Dr. Annan received BS degrees in History and Chemistry from West Chester University and a PhD with Paul Vouros in Analytical Chemistry from Northeastern University. Dr. Annan was a post doctoral associate in the lab of Klaus Biemann at MIT. He joined SmithKline Beecham Pharmaceuticals in 1992.
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