scholarly journals Identification of Small Molecular Weight Inhibitors of Src Homology 2 Domain-Containing Tyrosine Phosphatase 2 (SHP-2) via in Silico Database Screening Combined with Experimental Assay

2008 ◽  
Vol 51 (23) ◽  
pp. 7396-7404 ◽  
Author(s):  
Wen-Mei Yu ◽  
Olgun Guvench ◽  
Alexander D. MacKerell ◽  
Cheng-Kui Qu
Keyword(s):  
Molecular Weight ◽  
In Silico ◽  
Tyrosine Phosphatase ◽  
Small Molecular Weight ◽  
Src Homology 2 ◽  
Src Homology ◽  
Database Screening ◽  
Src Homology 2 Domain

scholarly journals Leishmania EF-1α Activates the Src Homology 2 Domain Containing Tyrosine Phosphatase SHP-1 Leading to Macrophage Deactivation

2002 ◽  
Vol 277 (51) ◽  
pp. 50190-50197 ◽  
Author(s):  
Devki Nandan ◽  
Taolin Yi ◽  
Martin Lopez ◽  
Crystal Lai ◽  
Neil E. Reiner
Keyword(s):  
Leishmania Donovani ◽  
Tyrosine Phosphatase ◽  
Elongation Factor ◽  
Host Protein ◽  
Src Homology 2 ◽  
Infected Cells ◽  
Src Homology ◽  
Src Homology 2 Domain

The human leishmaniasis are persistent infections of macrophages caused by protozoa of the genusLeishmania.The chronic nature of these infections is in part related to induction of macrophage deactivation, linked to activation of the Src homology 2 domain containing tyrosine phosphatase-1 (SHP-1) in infected cells. To investigate the mechanism of SHP-1 activation, lysates ofLeishmania donovanipromastigotes were subjected to SHP-1 affinity chromatography and proteins bound to the matrix were sequenced by mass spectrometry. This resulted in the identification ofLeishmaniaelongation factor-1α (EF-1α) as a SHP-1-binding protein. PurifiedLeishmaniaEF-1α, but not host cell EF-1α, bound directly to SHP-1in vitroleading to its activation. Three independent lines of evidence indicated thatLeishmaniaEF-1α may be exported from the phagosome thereby enabling targeting of host SHP-1. First, cytosolic fractions prepared from macrophages infected with [35S]methionine-labeled organisms containedLeishmaniaEF-1α. Second, confocal, fluorescence microscopy usingLeishmania-specific antisera detectedLeishmaniaEF-1α in the cytosol of infected cells. Third, co-immunoprecipitation showed thatLeishmaniaEF-1α was associated with SHP-1in vivoin infected cells. Finally, introduction of purifiedLeishmaniaEF-1α, but not the corresponding host protein into macrophages activated SHP-1 and blocked the induction of inducible nitric-oxide synthase expression in response to interferon-γ. Thus,LeishmaniaEF-1α is identified as a novel SHP-1-binding and activating protein that recapitulates the deactivated phenotype of infected macrophages.

scholarly journals Inhibitors of Src Homology-2 Domain Containing Protein Tyrosine Phosphatase-2 (Shp2) Based on Oxindole Scaffolds

2008 ◽  
Vol 51 (16) ◽  
pp. 4948-4956 ◽  
Author(s):  
Harshani R. Lawrence ◽  
Roberta Pireddu ◽  
Liwei Chen ◽  
Yunting Luo ◽  
Shen-Shu Sung ◽  
...  
Keyword(s):  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
Protein Tyrosine ◽  
Src Homology 2 ◽  
Src Homology ◽  
Src Homology 2 Domain
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