Protein kinase A (PKA)--a potential target for therapeutic intervention of dysfunctional immune cells.
In several cases of immunodeficiency and autoimmunity, the dysfunctional immune system is associated with either hypo- or hyperactive T and B cells. In autoimmune conditions such as systemic lupus erythematosus (SLE) and immunodeficiencies such as acquired immunodeficiency syndrome (AIDS), it has been demonstrated that the regulatory effect of the signaling pathway of cyclic 3', 5' adenosine monophosphate (cAMP) and cAMP-dependent protein kinase (PKA) is abrogated. PKA is well-known as a key regulator of immune responses in that it inhibits both early and late phases of antigen induced T and B cell activation. Here we will discuss a potential useful strategy for therapeutic interventions of dysfunctional T cells associated with SLE and HIV by modulation of the cAMP-PKA pathway. Therefore, we will describe the components and architecture of the cAMP-PKA signaling pathway in T cells in order to point out one or several steps which potentially may serve as targets for therapeutic intervention.
Skålhegg
Bjørn Steen
BS
Department of Nutrition, PO Box 1046 Blindern, 0316 Oslo, Norway. b.s.skalhegg@medisin.uio.no.
Funderud
Ane
A
Henanger
Heidi Hatledal
HH
Hafte
Tilahun Tolesa
TT
Larsen
Anja Camilla
AC
Kvissel
Anne-Katrine
AK
Eikvar
Sissel
S
Ørstavik
Sigurd
S
D054758:A Kinase Anchor Proteins; D048868:Adaptor Proteins, Signal Transducing / Q000502:physiology; D000262:Adenylyl Cyclases / Q000502:physiology; D000818:Animals; D000242:Cyclic AMP / Q000502:physiology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000502:physiology*; D003598:Cytoskeletal Proteins / Q000502:physiology; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy* / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects*; D010727:Phosphoric Diester Hydrolases / Q000187:drug effects / Q000502:physiology; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology*
D054758:A Kinase Anchor Proteins; C119719:AKAP9 protein, human; D048868:Adaptor Proteins, Signal Transducing; D003598:Cytoskeletal Proteins; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D010727:Phosphoric Diester Hydrolases; D000262:Adenylyl Cyclases