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 imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.
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.