Han-Mo Koo Seminar Series

Speaker: Kim Orth, Ph.D.
VAI Host:  Duesbery , Nick, Ph.D.
Speaker Affiliation: University of Texas Southwestern Medical Center
Speaker Title: Associate Professor, Department of Molecular Biology
Date: June 25, 2008
Time: 12:00 PM to 1:00 PM
Location: Van Andel Institute - Tomatis Auditorium

The causal agent of the bubonic plague is the microbial pathogen Yersinia pestis and, during infection, Yersinia evades phagocytosis, destroys the host defense response, and induces apoptosis in target host cells. These activities are efficiently carried about by a mere half dozen proteins called Yersinia outer proteins or Yops. The Yops mimic the activity of an eukaryoytic protein and use this activity to the pathogen’s advantage to debilitate the target cell. One of these proteins, YopJ, has been shown to not only block cytokine production but also promote apoptosis in the infected target host cell by preventing the activation of the superfamily of MAP Kinase Kinases, thereby, inhibiting both the MAP Kinase signaling pathways and the NFkB pathway. My lab discovered that YopJ uses a simple but elegant mechanism to inhibit the NFkB pathway and all MAPK signaling pathways. We showed that YopJ is an acetyltransferase that prevents the activation of eukaryotic MAPK kinases and IKKbeta by acetylating serine and/or threonine residues on the activation loop of these kinases, thereby preventing their activation by phosphorylation. This novel posttranslation modification of Ser/Thr acetylation directly competes with phosphorylation and attenuates signaling by changing the molecular message transduced by a modified residue. The discovery of Ser/Thr acetylation, as with tyrosine phosphorylation, presents a new paradigm for molecular signaling. Bacterial pathogens, like oncogenic viruses, usurp and mold eukaryotic activities so that they may be used during infection to manipulate signaling machinery in the eukaryotic host. The eukaryotic signaling machinery used for Ser/Thr acetylation, including enzymes, substrates and tools for identification, promises to provide new insights into biological signaling systems. The effector YopJ is one example from the enormous repertoire of bacterial effectors that my lab exploits to discover new mechanisms used to regulate eukaryotic signaling pathways.

My lab is also interested in the mechanisms used by another bacterial pathogen, Vibrio parahaemoylyticus. This pathogen contains two type III secretion systems and dozens of novel effectors. We are uncovering the molecular mechanisms used by this pathogen during infection.

In person attendance.

Van Andel Research Institute
Tomatis Auditorium
333 Bostwick Ave., N.E.
Grand Rapids, Michigan
49503

Online viewing.

Via webcast* at http://media.vai.org/vaichannel2
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*Participants viewing this webcast are not currently eligible for CME Accreditation; however, the Michigan State Medical Society is currently reviewing this process

“This activity has been planned and implemented in accordance with the Essential Areas and policies of the Michigan State Medical Society Committee on CME Accreditation through the joint sponsorship of the Grand Rapids Medical Education & Research Center for Health Professions and the Van Andel Research Institute. The Grand Rapids Medical Education & Research Center for Health Professions is accredited by the Michigan State Medical Society Committee on CME Accreditation to provide continuing medical education for physicians. The Grand Rapids Medical Education & Research Center for Health Professions designates this educational activity for a maximum of one Category 1 credit toward the AMA Physician’s Recognition Award. Each physician should claim only those credits that he/she actually spent in the activity.”

For more information please contact Laura Holman at (616) 234-5749