Overview of Common Cytokine Receptor gamma-Chain Family Cytokines
Cytokines belonging to the common cytokine receptor gamma chain family include IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21. Members of this family signal through receptor complexes that contain the common gamma chain subunit. This subunit associates with different cytokine-specific receptor subunits to form unique heterodimeric receptors for IL-4, IL-7, IL-9, and IL-21, or associates with both IL-2/IL-15 R beta and IL-2 R alpha or IL-15 R alpha to form heterotrimeric receptors for IL-2 or IL-15, respectively. Common gamma chain family cytokines generally activate three major signaling pathways that promote cellular survival and proliferation, the PI 3-K-Akt pathway, the RAS-MAPK pathway, and the JAK-STAT pathway.
Common gamma chain family cytokines serve as critical regulators of the development, survival, proliferation, differentiation and/or function of multiple immune cell types. These cytokines can have both unique and overlapping effects on different cell types, depending primarily on the expression patterns of the cytokines and their unique receptor subunits, and the activation of different STAT proteins. Inactivating mutations in the common gamma chain family cytokines, their receptors, or a subset of intracellular signaling molecules involved in these pathways can lead to severe immune system defects. The most common form of severe combined immunodeficiency, X-linked SCID, is caused by mutations in the common cytokine receptor gamma chain subunit.