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...

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Bibliographic Details
Published in:The Journal of immunology (1950) 1998-05, Vol.160 (9), p.4182-4189
Main Authors: Kaga, Shuji, Ragg, Scott, Rogers, Kem A, Ochi, Atsuo
Format: Article
Language:English
Subjects:
CD28 Antigens - immunology
CD3 Complex - immunology
Humans
Jurkat Cells
Lymphocyte Activation - immunology
MAP Kinase Kinase Kinase 1
p21-Activated Kinases
Protein-Serine-Threonine Kinases - immunology
Protein-Tyrosine Kinases - immunology
Signal Transduction - immunology
T-Lymphocytes - immunology
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Summary: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.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.160.9.4182