title: Modulation of T cell immune functions by the prostaglandin E(2)       - cAMP pathway in chronic inflammatory states.
abstract: Cyclic AMP is the intracellular second messenger for a variety of immunoregulatory inflammatory mediators such as prostaglandin E2, adenosine and histamine that signal to effector T cells from monocytes, macrophages and regulatory T cells. Protein kinase A (PKA) type I localizes to lipid rafts in effector T cells during T cell activation and directly modulates proximal signal events including phosphorylation of C-terminal Src kinase (Csk), which initiates a negative signal pathway that fine-tunes the T cell activation process. The PKA-Csk immunoregulatory pathway is scaffolded by the A kinase anchoring protein ezrin, the Csk binding protein phosphoprotein associated with glycosphingolipid-enriched membrane microdomains and the linker protein ezrin/radixin/moesin binding protein of 50 kDa. This pathway is hyperactivated in chronic infections with an inflammatory component such as HIV, other immunodeficiencies and around solid tumours as a consequence of local inflammation leading to inhibition of anti-tumour immunity. LINKED ARTICLES This article is part of a themed section on Novel cAMP Signalling Paradigms. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012.166.issue-2.
authors.affiliation: Centre for Molecular Medicine Norway, Nordic EMBL Partnership and Biotechnology Centre, University of Oslo, Oslo, Norway.
authors.forename: Kristoffer Watten
authors.initials: KW
authors.lastname: Brudvik
authors.forename: Kjetil
authors.initials: K
authors.lastname: Taskén
mesh_terms: D000818:Animals; D015179:Colorectal Neoplasms / Q000276:immunology; D000242:Cyclic AMP / Q000276:immunology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000276:immunology; D003598:Cytoskeletal Proteins / Q000276:immunology; D015232:Dinoprostone / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D000099149:Ezrin
chemical_list: D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D003598:Cytoskeletal Proteins; D015232:Dinoprostone; D000099149:Ezrin