Heterologous expression of a mammalian protein tyrosine phosphatase gene in Leishmania: effect on differentiation.
Leishmania is a protozoan pathogen which is transmitted to humans through the bite of an infected sandfly. This infection results in a spectrum of diseases throughout the developing world, collectively known as leishmaniasis. During its life cycle, Leishmania differentiates from the promastigote stage in the sandfly vector into the amastigote stage in the mammalian host where it multiplies exclusively in macrophage phagolysosomes. Although differentiation of Leishmania is essential for its survival and pathogenesis in the mammalian host, this process is poorly understood. In higher eukaryotic cells, protein tyrosine phosphorylation plays a central role in cell proliferation, differentiation and overall function. We have therefore investigated the role of protein tyrosine phosphorylation in Leishmania differentiation by undertaking complementary approaches to mediate protein tyrosine dephosphorylation in vivo. In the present study, L. donovani were engineered to express a mammalian protein tyrosine phosphatase, or were treated with inhibitors of protein tyrosine kinases, and the resulting phenotype was examined. Both approaches resulted in a partial differentiation from promastigotes to amastigotes including the expression of the amastigote specific A2 protein, morphological change and increased virulence. These data provide support for the involvement of tyrosine phosphorylation in the differentiation of Leishmania.
Nascimento
Mirna
M
Department of Microbiology of Microbiology and Immunology, 3775 University Street, McGill University, Montreal, Quebec, Canada, H3A 2B4.
Abourjeily
Nay
N
Ghosh
Anirban
A
Zhang
Wen Wei
WW
Matlashewski
Greg
G
D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007893:Leishmania donovani / Q000201:enzymology* / Q000235:genetics / Q000254:growth & development* / Q000472:pathogenicity; D007898:Leishmaniasis, Visceral / Q000469:parasitology / Q000503:physiopathology; D008264:Macrophages / Q000469:parasitology; D051379:Mice; D010766:Phosphorylation; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases / Q000235:genetics* / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D014443:Tyrosine; D014774:Virulence
D004791:Enzyme Inhibitors; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; C516607:PTPN1 protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases; C516609:Ptpn1 protein, mouse