Protein Kinase A (PKA) - A Potential Target for Therapeutic Intervention of Dysfunctional Immune Cells

B.   S.   Skalhegg; A.      Funderud; H.   H.   Henanger; T.   T.   Hafte; A.   C.   Larsen; A.-   K.   Kvissel; S.      Eikvar; S.      Orstavik

Abstract

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.

Keywords: camp-pka signaling pathway, adenylyl cyclases, receptor-g-protein, phosphodiesterases, post-translational modifications, hippocampus

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