Interleukin 10 receptor, alpha subunit explained

Interleukin-10 receptor subunit alpha is a subunit for the interleukin-10 receptor. IL10RA is its human gene.

IL10RA has also been designated CDw210a (cluster of differentiation w210a).

Function

See also: Akt/PKB signaling pathway. The protein encoded by this gene is a receptor for interleukin 10. This protein is structurally related to interferon receptors. It has been shown to mediate the immunosuppressive signal of interleukin 10, and thus inhibits the synthesis of proinflammatory cytokines. This receptor is reported to promote survival of myeloid progenitor cells through the insulin receptor substrate-2/PI 3-kinase/AKT pathway. Activation of this receptor leads to tyrosine phosphorylation of JAK1 and TYK2 kinases.^[1]

Interactions

Interleukin 10 receptor, alpha subunit has been shown to interact with:

• Interleukin 10^{[2] [3] [4] [5] [6]} and
• Janus kinase 1.^{[7] [8]}

Further reading

• Donnelly RP, Dickensheets H, Finbloom DS . The interleukin-10 signal transduction pathway and regulation of gene expression in mononuclear phagocytes . J. Interferon Cytokine Res. . 19 . 6 . 563–73 . 1999 . 10433356 . 10.1089/107999099313695 . 35958614 .
• Carson WE, Lindemann MJ, Baiocchi R, Linett M, Tan JC, Chou CC, Narula S, Caligiuri MA . The functional characterization of interleukin-10 receptor expression on human natural killer cells . Blood . 85 . 12 . 3577–85 . 1995 . 7540068 . 10.1182/blood.V85.12.3577.bloodjournal85123577. free .
• Ho AS, Wei SH, Mui AL, Miyajima A, Moore KW . Functional regions of the mouse interleukin-10 receptor cytoplasmic domain . Mol. Cell. Biol. . 15 . 9 . 5043–53 . 1995 . 7544437 . 230751 . 10.1128/mcb.15.9.5043.
• Tan JC, Braun S, Rong H, DiGiacomo R, Dolphin E, Baldwin S, Narula SK, Zavodny PJ, Chou CC . Characterization of recombinant extracellular domain of human interleukin-10 receptor . J. Biol. Chem. . 270 . 21 . 12906–11 . 1995 . 7759550 . 10.1074/jbc.270.21.12906 . free .
• Taniyama T, Takai S, Miyazaki E, Fukumura R, Sato J, Kobayashi Y, Hirakawa T, Moore KW, Yamada K . The human interleukin-10 receptor gene maps to chromosome 11q23.3 . Hum. Genet. . 95 . 1 . 99–101 . 1995 . 7814035 . 10.1007/BF00225083 . 205672 .
• Liu Y, Wei SH, Ho AS, de Waal Malefyt R, Moore KW . Expression cloning and characterization of a human IL-10 receptor . J. Immunol. . 152 . 4 . 1821–9 . 1994 . 10.4049/jimmunol.152.4.1821 . 8120391 . free .
• Ho AS, Liu Y, Khan TA, Hsu DH, Bazan JF, Moore KW . A receptor for interleukin 10 is related to interferon receptors . Proc. Natl. Acad. Sci. U.S.A. . 90 . 23 . 11267–71 . 1994 . 8248239 . 47963 . 10.1073/pnas.90.23.11267 . 1993PNAS...9011267H . free .
• Tan JC, Indelicato SR, Narula SK, Zavodny PJ, Chou CC . Characterization of interleukin-10 receptors on human and mouse cells . J. Biol. Chem. . 268 . 28 . 21053–9 . 1993 . 10.1016/S0021-9258(19)36892-9 . 8407942 . free .
• Lai CF, Ripperger J, Morella KK, Jurlander J, Hawley TS, Carson WE, Kordula T, Caligiuri MA, Hawley RG, Fey GH, Baumann H . Receptors for interleukin (IL)-10 and IL-6-type cytokines use similar signaling mechanisms for inducing transcription through IL-6 response elements . J. Biol. Chem. . 271 . 24 . 13968–75 . 1996 . 8662928 . 10.1074/jbc.271.24.13968 . free .
• Zdanov A, Schalk-Hihi C, Wlodawer A . Crystal structure of human interleukin-10 at 1.6 A resolution and a model of a complex with its soluble receptor . Protein Sci. . 5 . 10 . 1955–62 . 1997 . 8897595 . 2143256 . 10.1002/pro.5560051001 .
• Kotenko SV, Krause CD, Izotova LS, Pollack BP, Wu W, Pestka S . Identification and functional characterization of a second chain of the interleukin-10 receptor complex . EMBO J. . 16 . 19 . 5894–903 . 1997 . 9312047 . 1170220 . 10.1093/emboj/16.19.5894 .
• Hoover DM, Schalk-Hihi C, Chou CC, Menon S, Wlodawer A, Zdanov A . Purification of receptor complexes of interleukin-10 stoichiometry and the importance of deglycosylation in their crystallization . Eur. J. Biochem. . 262 . 1 . 134–41 . 1999 . 10231374 . 10.1046/j.1432-1327.1999.00363.x . free .
• Müschen A, Mirmohammadsadegh A, Jarzebska-Deussen B, Abts HF, Ruzicka T, Michel G . Differential IL-10 receptor gene expression in acute versus chronic atopic eczema. Modulation by immunosuppressive drugs and cytokines in normal cultured keratinocytes . Inflamm. Res. . 48 . 10 . 539–43 . 1999 . 10563471 . 10.1007/s000110050500 . 22779271 .
• Corinti S, Albanesi C, la Sala A, Pastore S, Girolomoni G . Regulatory activity of autocrine IL-10 on dendritic cell functions . J. Immunol. . 166 . 7 . 4312–8 . 2001 . 11254683 . 10.4049/jimmunol.166.7.4312 . free .
• Josephson K, Logsdon NJ, Walter MR . Crystal structure of the IL-10/IL-10R1 complex reveals a shared receptor binding site . Immunity . 15 . 1 . 35–46 . 2001 . 11485736 . 10.1016/S1074-7613(01)00169-8 . free .
• Crepaldi L, Gasperini S, Lapinet JA, Calzetti F, Pinardi C, Liu Y, Zurawski S, de Waal Malefyt R, Moore KW, Cassatella MA . Up-regulation of IL-10R1 expression is required to render human neutrophils fully responsive to IL-10 . J. Immunol. . 167 . 4 . 2312–22 . 2001 . 11490020 . 10.4049/jimmunol.167.4.2312 . free .
• Zhou JH, Broussard SR, Strle K, Freund GG, Johnson RW, Dantzer R, Kelley KW . IL-10 inhibits apoptosis of promyeloid cells by activating insulin receptor substrate-2 and phosphatidylinositol 3'-kinase . J. Immunol. . 167 . 8 . 4436–42 . 2001 . 11591769 . 10.4049/jimmunol.167.8.4436 . free .
• Josephson K, McPherson DT, Walter MR . Purification, crystallization and preliminary X-ray diffraction of a complex between IL-10 and soluble IL-10R1 . Acta Crystallogr. D . 57 . Pt 12 . 1908–11 . 2002 . 11717514 . 10.1107/S0907444901016249 .
• Wolk K, Kunz S, Asadullah K, Sabat R . Cutting edge: immune cells as sources and targets of the IL-10 family members? . J. Immunol. . 168 . 11 . 5397–402 . 2002 . 12023331 . 10.4049/jimmunol.168.11.5397 . free .

Notes and References

1. Web site: Entrez Gene: IL10RA interleukin 10 receptor, alpha.
2. Ho AS, Liu Y, Khan TA, Hsu DH, Bazan JF, Moore KW . A receptor for interleukin 10 is related to interferon receptors . Proc. Natl. Acad. Sci. U.S.A. . 90 . 23 . 11267–71 . December 1993 . 8248239 . 47963 . 10.1073/pnas.90.23.11267. 1993PNAS...9011267H . free .
3. Josephson K, Logsdon NJ, Walter MR . Crystal structure of the IL-10/IL-10R1 complex reveals a shared receptor binding site . Immunity . 15 . 1 . 35–46 . July 2001 . 11485736 . 10.1016/s1074-7613(01)00169-8. free .
4. Tan JC, Braun S, Rong H, DiGiacomo R, Dolphin E, Baldwin S, Narula SK, Zavodny PJ, Chou CC . Characterization of recombinant extracellular domain of human interleukin-10 receptor . J. Biol. Chem. . 270 . 21 . 12906–11 . May 1995 . 7759550 . 10.1074/jbc.270.21.12906. free .
5. Josephson K, McPherson DT, Walter MR . Purification, crystallization and preliminary X-ray diffraction of a complex between IL-10 and soluble IL-10R1 . Acta Crystallogr. D . 57 . Pt 12 . 1908–11 . December 2001 . 11717514 . 10.1107/s0907444901016249.
6. Hoover DM, Schalk-Hihi C, Chou CC, Menon S, Wlodawer A, Zdanov A . Purification of receptor complexes of interleukin-10 stoichiometry and the importance of deglycosylation in their crystallization . Eur. J. Biochem. . 262 . 1 . 134–41 . May 1999 . 10231374 . 10.1046/j.1432-1327.1999.00363.x. free .
7. Usacheva A, Sandoval R, Domanski P, Kotenko SV, Nelms K, Goldsmith MA, Colamonici OR . Contribution of the Box 1 and Box 2 motifs of cytokine receptors to Jak1 association and activation . J. Biol. Chem. . 277 . 50 . 48220–6 . December 2002 . 12374810 . 10.1074/jbc.M205757200 . free .
8. Usacheva A, Kotenko S, Witte MM, Colamonici OR . Two distinct domains within the N-terminal region of Janus kinase 1 interact with cytokine receptors . J. Immunol. . 169 . 3 . 1302–8 . August 2002 . 12133952 . 10.4049/jimmunol.169.3.1302. free .