http://purl.uniprot.org/citations/25786685 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
http://purl.uniprot.org/citations/25786685 | http://www.w3.org/2000/01/rdf-schema#comment | "Leishmania major is a parasite that resides and replicates in macrophages. We previously showed that the parasite enhanced CD40-induced Raf-MEK-ERK signaling but inhibited PI3K-MKK-p38MAPK signaling to proleishmanial effects. As Raf and PI3K have a Ras-binding domain but exert opposite effects on Leishmania infection, we examined whether Ras isoforms had differential roles in Leishmania infection. We observed that L. major enhanced N-Ras and H-Ras expression but inhibited K-Ras expression in macrophages. L. major infection enhanced N-Ras activity but inhibited H-Ras and K-Ras activity. TLR2 short hairpin RNA or anti-TLR2 or anti-lipophosphoglycan Abs reversed the L. major-altered N-Ras and K-Ras expressions. Pam3CSK4, a TLR2 ligand, enhanced N-Ras expression but reduced K-Ras expression, indicating TLR2-regulated Ras expression in L. major infection. Whereas N-Ras silencing reduced L. major infection, K-Ras and H-Ras silencing enhanced the infection both in macrophages in vitro and in C57BL/6 mice. BALB/c-derived macrophages transduced with lentivirally expressed N-Ras short hairpin RNA and pulsed with L. major-expressed MAPK10 enhanced MAPK10-specific Th1-type response. CD40-deficient mice primed with these macrophages had reduced L. major infection, accompanied by higher IFN-γ but less IL-4 production. As N-Ras is activated by Sos, a guanine nucleotide exchange factor, we modeled the N-Ras-Sos interaction and designed two peptides from their interface. Both the cell-permeable peptides reduced L. major infection in BALB/c mice but not in CD40-deficient mice. These data reveal the L. major-enhanced CD40-induced N-Ras activation as a novel immune evasion strategy and the potential for Ras isoform-targeted antileishmanial immunotherapy and immunoprophylaxis."xsd:string |
http://purl.uniprot.org/citations/25786685 | http://purl.org/dc/terms/identifier | "doi:10.4049/jimmunol.1401996"xsd:string |
http://purl.uniprot.org/citations/25786685 | http://purl.uniprot.org/core/author | "Kumari S."xsd:string |
http://purl.uniprot.org/citations/25786685 | http://purl.uniprot.org/core/author | "Nair A."xsd:string |
http://purl.uniprot.org/citations/25786685 | http://purl.uniprot.org/core/author | "Singh S."xsd:string |
http://purl.uniprot.org/citations/25786685 | http://purl.uniprot.org/core/author | "Srivastava A."xsd:string |
http://purl.uniprot.org/citations/25786685 | http://purl.uniprot.org/core/author | "Chakraborty S."xsd:string |
http://purl.uniprot.org/citations/25786685 | http://purl.uniprot.org/core/author | "Srivastava N."xsd:string |
http://purl.uniprot.org/citations/25786685 | http://purl.uniprot.org/core/author | "Pandey S.P."xsd:string |
http://purl.uniprot.org/citations/25786685 | http://purl.uniprot.org/core/author | "Saha B."xsd:string |
http://purl.uniprot.org/citations/25786685 | http://purl.uniprot.org/core/author | "Jha M.K."xsd:string |
http://purl.uniprot.org/citations/25786685 | http://purl.uniprot.org/core/author | "Krishnasastry M.V."xsd:string |
http://purl.uniprot.org/citations/25786685 | http://purl.uniprot.org/core/date | "2015"xsd:gYear |
http://purl.uniprot.org/citations/25786685 | http://purl.uniprot.org/core/name | "J Immunol"xsd:string |
http://purl.uniprot.org/citations/25786685 | http://purl.uniprot.org/core/pages | "3852-3860"xsd:string |
http://purl.uniprot.org/citations/25786685 | http://purl.uniprot.org/core/title | "Inhibition of CD40-induced N-Ras activation reduces leishmania major infection."xsd:string |
http://purl.uniprot.org/citations/25786685 | http://purl.uniprot.org/core/volume | "194"xsd:string |
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http://purl.uniprot.org/citations/25786685 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/25786685 |
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