Reactome | Interleukin-12 binds Interleukin-12 receptor

Interleukin-12 binds Interleukin-12 receptor

Stable Identifier

R-HSA-447226

Type

Reaction [binding]

Species

Homo sapiens

Compartment

plasma membrane, extracellular region, cytosol

ReviewStatus

5/5

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Interleukin-12 binds Interleukin-12 receptor

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Interleukin-12 (IL12) is a heterodimer of interleukin 12 alpha subunit (IL12A, IL-12p35) and interleukin 12 beta subunit (IL12B, IL-12p40) that binds the Interleukin 12 receptor, which is a heterodimer of Interleukin 12 receptor alpha subunit (IL12RB1) and Interleukin 12 beta subunit (IL12RB2) (Chua et al. 1994, Yoon et al. 2000, Chizzonite et al. 1992 , Gubler et al. 1991). The data from cross linking and surface labeling experiments suggest that only heterodimeric receptors bind IL12.
Dimerization of the receptor does not depend on IL12 binding to the receptor subunits but if the IL12 is pre-bound to either receptor subunit, the resulting binding pattern does not change (Chua et al. 1994).

Regulation:
IL12B monomer can be secreted and interact with the Interleukin 12 receptor. Human IL12B homodimers can be produced by cells containing expression constructs (Ling et al. 1995, Alloza & Vandenbroeck 2015) but not under natural conditions (Carra et al. 2000). IL12B homodimers do not mediate biological activity, rather they act as a competitive antagonist by competition with IL12 (Ling et al. 1995).

Literature References

PubMed ID	Title	Journal	Year
1578138	IL-12 receptor. I. Characterization of the receptor on phytohemagglutinin-activated human lymphoblasts Chizzonite, R, Truitt, T, Desai, BB, Nunes, P, Podlaski, FJ, Stern, AS, Gately, MK	J. Immunol.	1992
1674604	Coexpression of two distinct genes is required to generate secreted bioactive cytotoxic lymphocyte maturation factor Gubler, U, Chua, AO, Schoenhaut, DS, Dwyer, CM, McComas, W, Motyka, R, Nabavi, N, Wolitzky, AG, Quinn, PM, Familletti, PC	Proc Natl Acad Sci U S A	1991
7911493	Expression cloning of a human IL-12 receptor component. A new member of the cytokine receptor superfamily with strong homology to gp130 Chua, AO, Chizzonite, R, Desai, BB, Truitt, TP, Nunes, P, Minetti, LJ, Warrier, RR, Presky, DH, Levine, JF, Gately, MK	J. Immunol.	1994
10899108	Charged residues dominate a unique interlocking topography in the heterodimeric cytokine interleukin-12 Yoon, C, Johnston, SC, Tang, J, Stahl, M, Tobin, JF, Somers, WS	EMBO J	2000
7527811	Human IL-12 p40 homodimer binds to the IL-12 receptor but does not mediate biologic activity Ling, P, Gately, MK, Gubler, U, Stern, AS, Lin, P, Hollfelder, K, Su, C, Pan, YC, Hakimi, J	J. Immunol.	1995