Research ArticleHost-Pathogen Interactions

Leishmania GP63 Alters Host Signaling Through Cleavage-Activated Protein Tyrosine Phosphatases

Sci. Signal.  29 Sep 2009:
Vol. 2, Issue 90, pp. ra58
DOI: 10.1126/scisignal.2000213

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Exploiting the Host’s Phosphatases

Leishmaniasis is a globally important infectious disease caused by the parasite Leishmania. Gomez et al. show that infection of macrophages with Leishmania alters the activity of multiple protein tyrosine phosphatases (PTPs) through cleavage mediated by the parasite protein GP63. The activated PTPs inhibit macrophage inflammatory immune responses through dephosphorylation of Janus kinases. In addition to the PTP SHP-1, previously reported to be activated in response to Leishmania infection, Gomez et al. show that the PTPs TCPTP and PTP1B are also activated and that PTP1B serves a key role in the initial stages of disease progression in mice.