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

详细信息    查看全文

• 作者：Edward Helal Neto ; Ana Lú ; cia J. Coelho ; André ; Luiz Franco Sampaio ; Maria das Graç ; as M.O. Henriques ; Cezary Marcinkiewicz ; Marta S. De Freitas ; Christina Barja-Fidalgo
• 关键词：Disintegrin ; Integrin signaling ; Lymphocyte ; Proliferation ; Actin cytoskeleton ; FAK ; PI3K ; NF-κ ; B ; c-Fos
• 刊名：Biochimica et Biophysica Acta (BBA)/Molecular Cell Research
• 出版年：2007
• 出版时间：February 2007
• 年：2007
• 卷：1773
• 期：2
• 页码：176-184
• 全文大小：593 K

文摘

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 α₅β₁ and α_vβ₃, 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.