4dep

Structural highlights

Function

[IL1B_HUMAN] Produced by activated macrophages, IL-1 stimulates thymocyte proliferation by inducing IL-2 release, B-cell maturation and proliferation, and fibroblast growth factor activity. IL-1 proteins are involved in the inflammatory response, being identified as endogenous pyrogens, and are reported to stimulate the release of prostaglandin and collagenase from synovial cells.^[1] [IL1AP_HUMAN] Coreceptor with IL1R1. Associates with IL1R1 bound to IL1B to form the high affinity interleukin-1 receptor complex which mediates interleukin-1-dependent activation of NF-kappa-B and other pathways. Signaling involves the recruitment of adapter molecules such as TOLLIP, MYD88, and IRAK1 or IRAK2 via the respective TIR domains of the receptor/coreceptor subunits. Recruits TOLLIP to the signaling complex. Does not bind to interleukin-1 alone; binding of IL1RN to IL1R1, prevents its association with IL1R1 to form a signaling complex. The cellular response is modulated through a non-signaling association with the membrane IL1R2 decoy receptor. Secreted forms (isoforms 2 and 3) associate with secreted ligand-bound IL1R2 and increase the affinity of secreted IL1R2 for IL1B; this complex formation may be the dominant mechanism for neutralization of IL1B by secreted/soluble receptors.^{[2] [3] [4]} [IL1R1_HUMAN] Receptor for IL1A, IL1B and IL1RN. After binding to interleukin-1 associates with the corecptor IL1RAP to form the high affinity interleukin-1 receptor complex which mediates interleukin-1-dependent activation of NF-kappa-B, MAPK and other pathways. Signaling involves the recruitment of adapter molecules such as TOLLIP, MYD88, and IRAK1 or IRAK2 via the respective TIR domains of the receptor/coreceptor subunits. Binds ligands with comparable affinity and binding of antagonist IL1RN prevents association with IL1RAP to form a signaling complex.^[5]

See Also

• Interleukin
• Interleukin receptor

References

1. ↑ Van Damme J, De Ley M, Opdenakker G, Billiau A, De Somer P, Van Beeumen J. Homogeneous interferon-inducing 22K factor is related to endogenous pyrogen and interleukin-1. Nature. 1985 Mar 21-27;314(6008):266-8. PMID:3920526
2. ↑ Huang J, Gao X, Li S, Cao Z. Recruitment of IRAK to the interleukin 1 receptor complex requires interleukin 1 receptor accessory protein. Proc Natl Acad Sci U S A. 1997 Nov 25;94(24):12829-32. PMID:9371760
3. ↑ Jensen LE, Muzio M, Mantovani A, Whitehead AS. IL-1 signaling cascade in liver cells and the involvement of a soluble form of the IL-1 receptor accessory protein. J Immunol. 2000 May 15;164(10):5277-86. PMID:10799889
4. ↑ Smith DE, Hanna R, Della Friend, Moore H, Chen H, Farese AM, MacVittie TJ, Virca GD, Sims JE. The soluble form of IL-1 receptor accessory protein enhances the ability of soluble type II IL-1 receptor to inhibit IL-1 action. Immunity. 2003 Jan;18(1):87-96. PMID:12530978
5. ↑ Slack JL, Schooley K, Bonnert TP, Mitcham JL, Qwarnstrom EE, Sims JE, Dower SK. Identification of two major sites in the type I interleukin-1 receptor cytoplasmic region responsible for coupling to pro-inflammatory signaling pathways. J Biol Chem. 2000 Feb 18;275(7):4670-8. PMID:10671496
6. ↑ Thomas C, Bazan JF, Garcia KC. Structure of the activating IL-1 receptor signaling complex. Nat Struct Mol Biol. 2012 Mar 18;19(4):455-7. doi: 10.1038/nsmb.2260. PMID:22426547 doi:10.1038/nsmb.2260