Activation of human T lymphocytes via integrin signaling induced by RGD-disintegrins.
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 alpha(5)beta(1) and alpha(v)beta(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-kappaB 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.
Neto
Edward Helal
EH
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.
Coelho
Ana Lúcia J
AL
Sampaio
André Luiz Franco
AL
Henriques
Maria das Graças M O
Md
Marcinkiewicz
Cezary
C
De Freitas
Marta S
MS
Barja-Fidalgo
Christina
C
D000199:Actins / Q000378:metabolism; D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D002467:Cell Nucleus / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003599:Cytoskeleton / Q000187:drug effects; D019483:Disintegrins / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D006801:Humans; D016023:Integrins / Q000378:metabolism*; D037181:Lectins, C-Type; D008213:Lymphocyte Activation / Q000187:drug effects* / Q000276:immunology; D016328:NF-kappa B / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D019000:Phosphotyrosine / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology; D000099192:CD69 Antigens
D000199:Actins; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D019483:Disintegrins; D051416:Focal Adhesion Protein-Tyrosine Kinases; D016023:Integrins; D037181:Lectins, C-Type; D016328:NF-kappa B; D009842:Oligopeptides; D019869:Phosphatidylinositol 3-Kinases; D019000:Phosphotyrosine; D016760:Proto-Oncogene Proteins c-fos; D000099192:CD69 Antigens; C047981:arginyl-glycyl-aspartic acid