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. [unreadable] [unreadable]
NIH ExPorter
NIH ExPorter