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8.A.152.  The Interleukin Receptor (ILR) Family 

IL2R is the receptor for interleukin-2. This beta subunit is involved in receptor mediated endocytosis and transduces the mitogenic signals of IL2. Interleukin-2 is one of the critical cytokines that controls the proliferation and differentiation of cells of the immune system. Gesbert et al. 1998 reviewed the knowledge on the intracellular signaling events that convert the initial interaction of IL-2 with its receptor into pathways leading to various biological functions. A first step in IL-2 signaling is the activation of several protein tyrosine kinases that phosphorylate an array of intracellular substrates including the receptor complex. Phosphorylated tyrosine residues within the receptor then serve as docking sites for multimolecular signaling complexes that initiate three major pathways: the Jak-STAT pathway controlling gene transcription, the Ras-MAPK pathway leading to cell proliferation and gene transcription, and the PI3-kinase pathway involved in antiapoptotic signaling and organization of the cytoskeleton (Gesbert et al. 1998). Signaling through the interleukin-4 and interleukin-13 receptor complex regulates cholangiocyte TMEM16A (1.A.17.1.1) expression and biliary secretion (Dutta et al. 2020).

The receptor for interleukin-4 (IL4) and interleukin-13 (IL13), of 825 aas and 2 TMSs, one N-terminal and one about 30% from the N-terminus, and 427 aas and 2 TMSs, one N-terminal and one C-terminal, respectively. Signaling through the interleukin-4/interleukin-13 receptor complexes regulates cholangiocyte TMEM16A (TC# 1.A.17.1.1) expression and biliary secretion (Dutta et al. 2020). The IL4/IL13 responses are involved in regulating IgE production, and chemokine and mucus production at sites of allergic inflammation. In certain cell types, it can signal through activation of insulin receptor substrates, IRS1/IRS2 (Keegan et al. 1994).

References associated with 8.A.152 family:

Dutta, A.K., K. Boggs, A.K. Khimji, Y. Getachew, Y. Wang, C. Kresge, D.C. Rockey, and A.P. Feranchak. (2020). Signaling through the interleukin-4 and interleukin-13 receptor complexes regulates cholangiocyte TMEM16A expression and biliary secretion. Am. J. Physiol. Gastrointest Liver Physiol 318: G763-G771. 32090602
Gesbert, F., M. Delespine-Carmagnat, and J. Bertoglio. (1998). Recent advances in the understanding of interleukin-2 signal transduction. J Clin Immunol 18: 307-320. 9793823
Keegan, A.D., K. Nelms, M. White, L.M. Wang, J.H. Pierce, and W.E. Paul. (1994). An IL-4 receptor region containing an insulin receptor motif is important for IL-4-mediated IRS-1 phosphorylation and cell growth. Cell 76: 811-820. 8124718
Nagy, &.#.2.0.1.;., G. Mocsár, V. Sebestyén, J. Volkó, F. Papp, K. Tóth, S. Damjanovich, G. Panyi, T.A. Waldmann, A. Bodnár, and G. Vámosi. (2018). Membrane Potential Distinctly Modulates Mobility and Signaling of IL-2 and IL-15 Receptors in T Cells. Biophys. J. 114: 2473-2482. 29754714
Spangler, J.B., I. Moraga, J.L. Mendoza, and K.C. Garcia. (2015). Insights into cytokine-receptor interactions from cytokine engineering. Annu Rev Immunol 33: 139-167. 25493332