Yersinia pestis, the causative agent of plague, frequently results in fatal infections. Understanding the molecular mechanisms of bacterial pathogenesis has become increasingly important due to the recent concerns about bioterrorism and the development of measures to counteract these infectious agents. Yersinia injects effector proteins into host cells to inactivate the host immune response. One effector, YopM, is necessary for Yersinia virulence, but how this protein functions in host cells is unknown. The overall aim of this proposal is to identify the molecular mechanisms of how YopM contributes to the virulence of Yersinia. In this research proposal, protein kinase C-like 2 (PRK2) is identified as the first intracellular target of YopM. PRK2 is a serine/threonine kinase that has been implicated in regulation of apoptosis modulation of the actin cytoskeleton, and as a downstream effector of receptor tyrosine kinases. These studies of YopM will determine how the interaction of YopM with PRK2 alters PRK2 kinase activity, affects cellular signaling pathways, characterize the interaction of these proteins by biochemical and crystallographic approaches, as well as examine the conservation of these functions in structurally similar proteins from other bacteria. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32AI054053-02
Application #
6757262
Study Section
Special Emphasis Panel (ZRG1-F08 (20))
Program Officer
Schaefer, Michael R
Project Start
2003-06-01
Project End
2006-05-31
Budget Start
2004-06-01
Budget End
2005-05-31
Support Year
2
Fiscal Year
2004
Total Cost
$48,928
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Biochemistry
Type
Schools of Medicine
DUNS #
073133571
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
McDonald, Christine; Chen, Felicia F; Ollendorff, Vincent et al. (2005) A role for Erbin in the regulation of Nod2-dependent NF-kappaB signaling. J Biol Chem 280:40301-9