Interleukin-12 subunit alpha

Definition:

Heterodimerizes with IL12B to form the IL-12 cytokine or with EBI3/IL27B to form the IL-35 cytokine. IL-12 is primarily produced by professional antigen-presenting cells (APCs) such as B-cells and dendritic cells (DCs) as well as macrophages and granulocytes and regulates T-cell and natural killer-cell responses, induces the production of interferon-gamma (IFN-gamma), favors the differentiation of T-helper 1 (Th1) cells and is an important link between innate resistance and adaptive immunity. Mechanistically, exerts its biological effects through a receptor composed of IL12R1 and IL12R2 subunits. Binding to the receptor results in the rapid tyrosine phosphorylation of a number of cellular substrates including the JAK family kinases TYK2 and JAK2. In turn, recruited STAT4 gets phosphorylated and translocates to the nucleus where it regulates cytokine/growth factor responsive genes. As part of IL-35, plays essential roles in maintaining the immune homeostasis of the liver microenvironment and functions also as an immune-suppressive cytokine (By similarity). Mediates biological events through unconventional receptors composed of IL12RB2 and gp130/IL6ST heterodimers or homodimers. Signaling requires the transcription factors STAT1 and STAT4, which form a unique heterodimer that binds to distinct DNA sites.

References:

[1]. Lauren W Collison, et al. The composition and signaling of the IL-35 receptor are unconventional. Nat Immunol. 2012 Feb 5;13(3):290-9. [Content Brief]

[2]. C M Bacon, et al. Interleukin 12 induces tyrosine phosphorylation and activation of STAT4 in human lymphocytes. Proc Natl Acad Sci U S A. 1995 Aug 1;92(16):7307-11. [Content Brief]

[3]. D H Presky, et al. A functional interleukin 12 receptor complex is composed of two beta-type cytokine receptor subunits. Proc Natl Acad Sci U S A. 1996 Nov 26;93(24):14002-7. [Content Brief]

[4]. U Gubler, et al. Coexpression of two distinct genes is required to generate secreted bioactive cytotoxic lymphocyte maturation factor. Proc Natl Acad Sci U S A. 1991 May 15;88(10):4143-7. [Content Brief]

[5]. C Heufler, et al. Interleukin-12 is produced by dendritic cells and mediates T helper 1 development as well as interferon-gamma production by T helper 1 cells. Eur J Immunol. 1996 Mar;26(3):659-68. [Content Brief]

[6]. C M Bacon, et al. Interleukin 12 (IL-12) induces tyrosine phosphorylation of JAK2 and TYK2: differential use of Janus family tyrosine kinases by IL-2 and IL-12. J Exp Med. 1995 Jan 1;181(1):399-404. [Content Brief]

[7]. S F Wolf, et al. Cloning of cDNA for natural killer cell stimulatory factor, a heterodimeric cytokine with multiple biologic effects on T and natural killer cells. J Immunol. 1991 May 1;146(9):3074-81. [Content Brief]

[8]. A S Stern, et al. Purification to homogeneity and partial characterization of cytotoxic lymphocyte maturation factor from human B-lymphoblastoid cells. Proc Natl Acad Sci U S A. 1990 Sep;87(17):6808-12. [Content Brief]

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