cAMP inhibits Src-family kinase signalling by PKA (protein kinase A)-mediated phosphorylation and activation of Csk (C-terminal Src kinase). The PKA type I–Csk pathway is assembled and localized in membrane microdomains (lipid rafts) and regulates immune responses activated through the TCR (T-cell receptor). PKA type I is targeted to the TCR–CD3 complex during T-cell activation via an AKAP (A-kinase-anchoring protein) that serves as a scaffold for the cAMP–PKA/Csk pathway in lipid rafts of the plasma membrane during T-cell activation. Displacement of PKA by anchoring disruption peptides prevents cAMP/PKA type I-mediated inhibition of T-cell activation. These findings provide functional evidence that PKA type I regulation of T-cell responses is dependent on AKAP anchoring. Furthermore, we show that upon TCR/CD28 co-ligation, β-arrestin in complex with PDE4 (phosphodiesterase 4) is recruited to lipid rafts. The CD28-mediated recruitment of PDE4 to lipid rafts potentiates T-cell immune responses and counteracts the local, TCR-induced production of cAMP that produces negative feedback in the absence of a co-receptor stimulus. The specific recruitment of PDE4 thus serves to abrogate the negative feedback by cAMP which is elicited in the absence of a co-receptor stimulus.
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August 2006
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Conference Article|
July 21 2006
The molecular machinery for cAMP-dependent immunomodulation in T-cells
K. Taskén;
K. Taskén
1
1The Biotechnology Centre of Oslo, University of Oslo, P.O. Box 1125, Blindern, N-0317 Oslo, Norway
1To whom correspondence should be addressed (email kjetil.tasken@biotek.uio.no).
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A.J. Stokka
A.J. Stokka
1The Biotechnology Centre of Oslo, University of Oslo, P.O. Box 1125, Blindern, N-0317 Oslo, Norway
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Biochem Soc Trans (2006) 34 (4): 476–479.
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Received:
March 27 2006
Citation
K. Taskén, A.J. Stokka; The molecular machinery for cAMP-dependent immunomodulation in T-cells. Biochem Soc Trans 1 August 2006; 34 (4): 476–479. doi: https://doi.org/10.1042/BST0340476
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