Activation of human T lymphocytes via integrin signaling induced by RGD-disintegrins

• Published in: Biochimica et biophysica acta 2007-02, Vol.1773 (2), p.176-184
• Main Authors: Neto, Edward Helal, Coelho, Ana Lúcia J., Sampaio, André Luiz Franco, Henriques, Maria das Graças M.O., Marcinkiewicz, Cezary, De Freitas, Marta S., Barja-Fidalgo, Christina
• Format: Article
• Language: English
• Subjects: Actin cytoskeleton; Actins - metabolism; Animals; Antigens, CD - immunology; Antigens, Differentiation, T-Lymphocyte - immunology; c-Fos; Cell Nucleus - drug effects; Cell Proliferation - drug effects; Cytoskeleton - drug effects; Disintegrin; Disintegrins - pharmacology; Enzyme Activation - drug effects; FAK; Focal Adhesion Protein-Tyrosine Kinases - metabolism; Humans; Integrin signaling; Integrins - metabolism; Lectins, C-Type; Lymphocyte; Lymphocyte Activation - drug effects; Lymphocyte Activation - immunology; NF-kappa B - metabolism; NF-κB; Oligopeptides - pharmacology; Phosphatidylinositol 3-Kinases - metabolism; Phosphotyrosine - metabolism; PI3K; Proliferation; Protein Binding - drug effects; Protein Transport - drug effects; Proto-Oncogene Proteins c-fos - metabolism; Signal Transduction - drug effects; T-Lymphocytes - cytology; T-Lymphocytes - drug effects; T-Lymphocytes - enzymology; T-Lymphocytes - immunology
• ISSN: 0167-4889; 0006-3002; 1879-2596
• DOI: 10.1016/j.bbamcr.2006.09.026

Adhesive interactions play important roles in coordinating T cell migration and activation, which are mediated by binding of integrins to RGD motif found on extracellular matrix proteins. Disintegrins, isolated from snake venoms, contain the RGD sequence that confers selectivity to integrin interaction. We have investigated the ability of three RGD-disintegrins, ligands of α 5β 1 and α vβ 3, Flavoridin (Fl), Kistrin (Kr) and Echistatin (Ech), in modulating the activation of human T lymphocyte. The disintegrins induced T cell proliferation and CD69 expression. This activation parallels with actin cytoskeleton reorganization and tyrosine phosphorylation. Furthermore, the peptides induced focal adhesion kinase (FAK) and phosphoinositide 3-kinase (PI3K) activation. Finally, RGD-disintegrins were capable of driving NF-κB nuclear translocation and c-Fos expression, in a PI3K and ERK1/2 activities dependent manner. This report is the first to show that RGD-disintegrins interact with integrins on human T lymphocyte surface, modulating cell proliferation and activation of specific pathways coupled to integrin receptor.