Activation of p21-CDC42/Rac-activated kinases by CD28 signaling: p21-activated kinase (PAK) and MEK kinase 1 (MEKK1) may mediate the interplay between CD3 and CD28 signals.
CD28, a T cell costimulatory receptor, provides a signal that induces both optimal proliferation and the production of IL-2 by TCR-activated T cells. We show that the stimulation of CD28 leads to the activation of p21-activated kinase and MEK kinase 1. The same pathway was also stimulated in T cells treated with the cell-permeable ceramide analogue, C2-ceramide. The combined stimulation of either CD3 and CD28 or CD3 concurrently with C2-ceramide largely enhanced the activity of p21-activated kinase and MEK kinase 1. Therefore the Rac1/CDC42-coupled pathway(s) is a candidate that transduces and facilitates cross-talk between the CD28 costimulatory signal and the TCR signal.
Kaga
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John P. Robarts Research Institute, The Department of Microbiology and Immunology, The University of Western Ontario, London, Canada.
Ragg
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Rogers
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Ochi
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D018106:CD28 Antigens / Q000276:immunology*; D017252:CD3 Complex / Q000276:immunology*; D006801:Humans; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000276:immunology; D048728:MAP Kinase Kinase Kinase 1; D017346:Protein Serine-Threonine Kinases / Q000276:immunology*; D011505:Protein-Tyrosine Kinases / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D054462:p21-Activated Kinases
D018106:CD28 Antigens; D017252:CD3 Complex; D011505:Protein-Tyrosine Kinases; C515911:PAK3 protein, human; D017346:Protein Serine-Threonine Kinases; D054462:p21-Activated Kinases; D048728:MAP Kinase Kinase Kinase 1; C482576:MAP3K1 protein, human