Recombinant Human Interleukin-12 subunit alpha (IL12A)

Function

Heterodimerizes with IL12B to form the IL-12 cytokine or with EBI3/IL27B to form the IL-35 cytokine (PubMed:8605935, PubMed:8943050). 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 (PubMed:1673147, PubMed:1674604, PubMed:8605935). Mechanistically, exerts its biological effects through a receptor composed of IL12R1 and IL12R2 subunits (PubMed:8943050). Binding to the receptor results in the rapid tyrosine phosphorylation of a number of cellular substrates including the JAK family kinases TYK2 and JAK2 (PubMed:7528775). In turn, recruited STAT4 gets phosphorylated and translocates to the nucleus where it regulates cytokine/growth factor responsive genes (PubMed:7638186). As part of IL-35, plays essential roles in maintaining the immune homeostasis of the liver microenvironment and also functions as an immune-suppressive cytokine (By similarity). Mediates biological events through unconventional receptors composed of IL12RB2 and gp130/IL6ST heterodimers or homodimers (PubMed:22306691). Signaling requires the transcription factors STAT1 and STAT4, which form a unique heterodimer that binds to distinct DNA sites (PubMed:22306691)

Subcellular Location

Secreted

Subunit

Heterodimer with IL12B; disulfide-linked (PubMed:10899108, PubMed:1674604). This heterodimer is known as interleukin IL-12 (PubMed:1674604). Heterodimer with EBI3/IL27B; not disulfide-linked (PubMed:9342359). This heterodimer is known as interleukin IL-35 (PubMed:9342359). Interacts with NBR1; this interaction promotes IL-12 secretion (By similarity)

• Wolf S.F. 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)
• Gubler U. 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)
• PubMed: CI-6O51548LOBJPC (JUL-)
• Muzny D.M. et al. The DNA sequence, annotation and analysis of human chromosome 3. — Nature (2006)
• Stern A.S. 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)
• Merberg D.M. et al. Sequence similarity between NKSF and the IL-6/G-CSF family. — Immunol. Today (1992)
• Bacon C.M. 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)
• Bacon C.M. et al. Interleukin 12 induces tyrosine phosphorylation and activation of STAT4 in human lymphocytes. — Proc. Natl. Acad. Sci. U.S.A. (1995)