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.
Department of Immunology and Cell Biology, Research Center Borstel, Germany. sbulfone@fz-borstel.de
Silvia
S
Bulfone-Paus
Elena
E
Bulanova
Vadim
V
Budagian
Ralf
R
Paus
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