The interleukin-15/interleukin-15 receptor system as a model for juxtacrine and reverse signaling.
Interleukin-15 (IL-15) is a pleiotropic cytokine of the 4 alpha-helix bundle family, which binds to a receptor complex that displays common elements with the IL-2 receptor and a unique high-affinity alpha chain. This review focuses on juxtacrine and reverse signaling levels in the IL-15/IL-15R system. Specifically, we discuss how agonistic stimulation of membrane-bound IL-15 induces phosphorylation of members of the MAP kinase family and of focal adhesion kinase (FAK), thereby upregulating processes including cytokine secretion, cell adhesion and migration. In addition, we explore IL-15 trans-presentation and intracellular signaling, and define promising molecular targets for future pharmacological intervention in infectious diseases and immunological disorders. These frontiers in IL-15/IL-15Ralpha research serve as highly instructive examples for key concepts, unsolved problems and therapeutic opportunities in juxtacrine and reverse signaling in general.
Bulfone-Paus
Silvia
S
Department of Immunology and Cell Biology, Research Center Borstel, Germany. sbulfone@fz-borstel.de
Bulanova
Elena
E
Budagian
Vadim
V
Paus
Ralf
R
D000818:Animals; D006801:Humans; D019409:Interleukin-15 / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological; D019899:Paracrine Communication; D053647:Receptors, Interleukin-15; D015375:Receptors, Interleukin-2 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
C508024:IL15RA protein, human; D019409:Interleukin-15; D053647:Receptors, Interleukin-15; D015375:Receptors, Interleukin-2