IMR Press / FBL / Volume 11 / Issue 3 / DOI: 10.2741/2022

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Article
Negative regulation of T-cell receptor activation by the cAMP-PKA-Csk signalling pathway in T-cell lipid rafts
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1 Biotechnology Centre of Oslo, University of Oslo, N-0317 Oslo, Norway
Academic Editor:Antonio Sechi
Front. Biosci. (Landmark Ed) 2006, 11(3), 2929–2939;
Published: 1 September 2006

Spatial organization of signal proteins in specialized cholesterol and glycosphingolipid-enriched microdomains (lipid rafts) provide specificity in lymphocyte signalling. Src kinases associate with lipid rafts on the basis of their dual acylation in the N-terminus and initiate T cell signalling. The immunomodulatory signal enzyme protein kinase A (PKA) is a serine/threonine kinase that controls a number of processes important for immune activation by phosphorylation of substrates that alters protein-protein interactions or changes the enzymatic activity of target proteins in T cells. PKA substrates involved in immune activation include transcription factors, members of the MAP kinase pathway, phospholipases and the Src kinase Csk. The PKA type I isoenzyme localizes to lipid rafts during T cell activation and modulates directly the proximal events that take place after engagement of the T cell receptor. The most proximal and major target for PKA phosphorylation is the C-terminal Src kinase Csk which initiates a negative signal pathway that fine-tunes the T cell activation process.

Immune system
T cell
Lipid Raft
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