title: Leishmania donovani engages in regulatory interference by targeting macrophage protein tyrosine phosphatase SHP-1.
abstract: Protozoan parasites of the genus leishmania are obligate intracellular parasites of monocytes and macrophages. These pathogens have evolved to invade the mammalian immune system and typically survive for long periods of time. Leishmania have developed a variety of remarkable strategies to prevent their elimination by both innate and acquired immune effector mechanisms. One particular strategy of interest involves manipulation of host cell regulatory pathways so as to prevent macrophage activation required for efficient microbicidal activity. These interference mechanisms are the main focus of this review. Several lines of evidence have been developed to show that the Src homology-2 domain containing tyrosine phosphatase-1 (SHP-1) becomes activated in leishmania-infected cells and that this contributes to disease pathogenesis. Recent studies aimed at understanding the mechanism responsible for the change in activation state of SHP-1 led to the identification of leishmania EF-1alpha as an SHP-1 binding protein and SHP-1 activator. This was a surprising finding given that this ubiquitous and highly conserved protein plays an essential role in protein translation in both prokaryotic and eukaryotic cells. The role of leishmania EF-1alpha as an SHP-1 activator and its contribution to pathogenesis are reviewed with particular attention to the properties that distinguish it from host EF-1alpha.
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Vancouver Coastal Health Research Institute (VCHRI), The University of British Columbia, Room 452D, 2733 Heather Street, Vancouver, BC, Canada, V5Z 3J5. dnandan@interchange.ubc.ca
authors.forename: Devki
authors.initials: D
authors.lastname: Nandan
authors.forename: Neil E
authors.initials: NE
authors.lastname: Reiner
mesh_terms: D000818:Animals; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D007893:Leishmania donovani / Q000472:pathogenicity*; D007898:Leishmaniasis, Visceral / Q000378:metabolism*; D008264:Macrophages / Q000201:enzymology / Q000469:parasitology* / Q000502:physiology*; D020648:Peptide Elongation Factor 1 / Q000037:antagonists & inhibitors / Q000502:physiology; D054645:Protein Phosphatase 1; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D020648:Peptide Elongation Factor 1; D054645:Protein Phosphatase 1; C509249:PTPN6 protein, human; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases