Novel mechanism of signaling by CD28.
Ligation of both the T cell receptor (TCR) and the CD28 receptor is required for full T cell activation to occur. Engagement of the TCR in primary T cells is followed by rapid cAMP production in lipid rafts and activation of the cAMP-protein kinase A (PKA)-Csk pathway inhibiting proximal T cell signaling. However, CD28 stimulation leads to recruitment of a beta-arrestin/phosphodiesterase-4 (PDE4) complex to rafts, resulting in down-regulation of cAMP levels. Thus, the activities of both PKA and PDE4 seem to be important for regulation of TCR-induced signaling and T cell function. This review will focus on the novel mechanism whereby CD28 through PI3K regulates recruitment of a PKB/beta-arrestin/PDE4 complex thereby allowing a complete T cell activation to proceed.
Bjørgo
Elisa
E
The Biotechnology Centre of Oslo and Centre for Molecular Medicine Norway, Nordic EMBL Partnership, University of Oslo, P.O. Box 1125, Blindern, N-0317 Oslo, Norway.
Taskén
Kjetil
K
D000818:Animals; D019390:Arrestins / Q000378:metabolism; D018106:CD28 Antigens / Q000276:immunology / Q000378:metabolism*; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4 / Q000378:metabolism; D006801:Humans; D008213:Lymphocyte Activation; D021962:Membrane Microdomains / Q000276:immunology*; D046912:Multiprotein Complexes / Q000276:immunology*; D011494:Protein Kinases / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology*; D013601:T-Lymphocytes / Q000378:metabolism* / Q000473:pathology; D000071557:beta-Arrestins
D019390:Arrestins; D018106:CD28 Antigens; D046912:Multiprotein Complexes; D011948:Receptors, Antigen, T-Cell; D000071557:beta-Arrestins; D011494:Protein Kinases; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4