title: Involvement of phosphatidylinositol-3 kinase-Akt and nuclear factor kappa-B pathways in the effect of frutalin on human lymphocyte.
abstract: The mechanisms involved in the mitogenic effect of lectins are not fully understood and are thought to involve a cascade of intracellular signals related to T cell receptor activation. This study shows that frutalin, the alpha-D-galactose-binding lectin from Artocarpus incisa seeds, is a potent mitogenic activator of human lymphocytes. This effect is inhibited by D-galactose and PI3K inhibitors, and is accompanied by an increase in IL-2 receptor expression and by a PI3K-dependent IL-2 gene expression and IL-2 protein synthesis. Frutalin also induces Akt-phosphorylation and activates NF-kappaB, inducing its translocation from the cytosol to the nucleus. Both effects are blocked in the presence of D-galactose or by PI3K inhibitors. In summary, frutalin, interacting with alpha-D-galactose, activates signaling pathways related to TCR, and thereby triggers PI3K/Akt and NF-kappaB pathway, which modulates T cell proliferation, IL-2 synthesis and IL-2R expression. Frutalin might be a useful tool to study intracellular mechanisms following T cell activation that link upstream signaling pathways to downstream events.
authors.affiliation: Departamento de Farmacologia, Instituto de Biologia, Universidade do Estado do Rio de Janeiro, Av. 28 de setembro 87 fds, Vila Isabel, Rio de Janeiro, 20551-030, RJ, Brazil.
authors.forename: Aline C
authors.initials: AC
authors.lastname: Brando-Lima
authors.forename: Roberta F
authors.initials: RF
authors.lastname: Saldanha-Gama
authors.forename: Cristiane Ribeiro
authors.initials: CR
authors.lastname: Pereira
authors.forename: Christina Gaspar
authors.initials: CG
authors.lastname: Villela
authors.forename: André Luiz Franco
authors.initials: AL
authors.lastname: Sampaio
authors.forename: Ana C O
authors.initials: AC
authors.lastname: Monteiro-Moreira
authors.forename: Maria das Graças M O
authors.initials: Md
authors.lastname: Henriques
authors.forename: Renato A
authors.initials: RA
authors.lastname: Moreira
authors.forename: Christina
authors.initials: C
authors.lastname: Barja-Fidalgo
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D031622:Artocarpus; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis / Q000235:genetics; D008214:Lymphocytes / Q000187:drug effects* / Q000201:enzymology; D008934:Mitogens / Q000494:pharmacology; D016328:NF-kappa B / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D037121:Plant Lectins / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology*; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis / Q000235:genetics; D012639:Seeds; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology*
chemical_list: D007376:Interleukin-2; D008934:Mitogens; D016328:NF-kappa B; D037121:Plant Lectins; D015375:Receptors, Interleukin-2; C043696:jacalin; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt