The modulation of CD40 ligand signaling by transmembrane CD28 splice variant in human T cells.
The role of CD40 ligand (CD40L)/CD40 signaling in T cell-dependent B cell differentiation and maturation has been amply documented. The mechanism of CD40 signaling in B cells has been well established, whereas the signaling mechanism of CD40L in T cell costimulation remains unknown. In this study we show that CD28i, a transmembrane splice variant of CD28 costimulatory receptor, complexes with CD40L in human T cells. The cross-linking of CD40L resulted in the coendocytosis of CD28i with CD40L. The tyrosine phosphorylation of CD28i followed the cross-linking of CD40L, and the overexpression of CD28i augmented the c-Jun NH2-terminal kinase, p21-activated kinase 2, and nuclear factor kappaB activation. These data indicate that CD28i, by functioning as a signaling adaptor, transduces CD40L signaling as well as CD28 signaling in human T cells.
Mikolajczak
Sebastian A
SA
University Health Network, Toronto, Ontario M5G 2C4, Canada.
Ma
Bruce Y
BY
Yoshida
Tetsuya
T
Yoshida
Ryoko
R
Kelvin
David J
DJ
Ochi
Atsuo
A
D017398:Alternative Splicing; D018106:CD28 Antigens / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D023201:CD40 Ligand / Q000737:chemistry / Q000378:metabolism*; D002460:Cell Line; D003432:Cross-Linking Reagents; D004705:Endocytosis; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D054462:p21-Activated Kinases
D018106:CD28 Antigens; D003432:Cross-Linking Reagents; D016328:NF-kappa B; D023201:CD40 Ligand; C515907:PAK2 protein, human; D017346:Protein Serine-Threonine Kinases; D054462:p21-Activated Kinases; D020928:Mitogen-Activated Protein Kinases