[The adaptor protein Lnk modulates endothelial cell activation].
Lnk is an adaptator protein involved in B lymphocytes and platelet differentiation and in T lymphocyte activation. We previously reported on Lnk expression and regulation in endothelial cells (ECs) upon activation. In the present study, the involvement of Lnk in the tumor necrosis factor alpha (TNFalpha) pathway was investigated in vitro through Lnk overexpression in primary cultures of human endothelial cells. Using a recombinant adenovirus encoding human Lnk, we first demonstrated that Lnk overexpression does not induce vascular cell adhesion molecule-1 (VCAM-1) suggesting that Lnk does not promote ECs activation. However, Lnk overexpression significantly reduced TNFalpha-mediated expression of VCAM-1 (at mRNA and protein levels) in activated EC as compared with controls. Western blot analysis showed that Lnk overexpression in HUVEC was associated with phosphorylation of Akt kinase (at Ser 473) with no effect on IkappaBalpha, the specific inhibitor of NFkappaB, indicating that Lnk promotes activation of the phosphatidylinositol 3-kinase (PI3-kinase) pathway in ECs. Altogether, these results suggest that, in ECs, Lnk may participate to a regulatory pathway involving the PI3-kinase and modulating the inflammatory response.
Fitau
Juliette
J
Institut national de la santé et de la recherche médicale, UMR 643, Immunointervention en allo et xénotransplantation, et institut de transplantation et de recherche en transplantation, CHU Hôtel-Dieu, 44093 Nantes cedex 01, France.
Boulday
Gwénola
G
Coulon
Flora
F
Charreau
Béatrice
B
D048868:Adaptor Proteins, Signal Transducing; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000502:physiology*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011506:Proteins / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis
D048868:Adaptor Proteins, Signal Transducing; D047908:Intracellular Signaling Peptides and Proteins; D019869:Phosphatidylinositol 3-Kinases; D011506:Proteins; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; C490778:SH2B3 protein, human