Molecular mechanisms for protein kinase A-mediated modulation of immune function.
Protein kinase A (PKA) is a serine/threonine kinase that regulates a number of cellular processes important for immune activation and control. Modulation of signal transduction by PKA is a complex and diverse process, and differential isozyme expression, holoenzyme composition and subcellular localization contribute specificity to the PKA signalling pathway. In lymphocytes, phosphorylation by PKA has been demonstrated to regulate antigen receptor-induced signalling both by altering protein-protein interactions and by changing the enzymatic activity of target proteins. PKA substrates involved in immune activation include transcription factors, members of the MAP kinase pathway and phospholipases. The ability of PKA type I to regulate activation of signalling components important for formation of the immunological synapse, demonstrates that the cAMP signalling pathway can directly modulate proximal events in lymphocyte activation. Furthermore, the recent discovery that PKA regulates Src kinases through modulation of Csk, supports the notion that PKA is involved in the fine-tuning of immune receptor signalling in lipid rafts.
Torgersen
Knut Martin
KM
Department of Medical Biochemistry, Institute of Basic Medical Sciences, University of Oslo, P.O. Box 1112, Blindern, N-0317 Oslo, Norway.
Vang
Torkel
T
Abrahamsen
Hilde
H
Yaqub
Sheraz
S
Taskén
Kjetil
K
D000081247:CSK Tyrosine-Protein Kinase; D017074:Common Variable Immunodeficiency / Q000201:enzymology / Q000276:immunology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology*; D015658:HIV Infections / Q000201:enzymology / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation; D021962:Membrane Microdomains / Q000201:enzymology; D008954:Models, Biological; D011505:Protein-Tyrosine Kinases / Q000502:physiology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000201:enzymology / Q000276:immunology*; D019061:src-Family Kinases
D011948:Receptors, Antigen, T-Cell; D011505:Protein-Tyrosine Kinases; D000081247:CSK Tyrosine-Protein Kinase; D019061:src-Family Kinases; C000631346:CSK protein, human; D017868:Cyclic AMP-Dependent Protein Kinases