Measured in a cell proliferation assay using PHA-stimulated human T lymphoblasts. Symons, J.A. et al. (1987) in Lymphokines and Interferons, a Practical Approach. Clemens, M.J. et al. (eds): IRL Press. 272. The ED50 for this effect is 0.07-0.3 ng/mL.
Chinese Hamster Ovary cell line, CHO-derived rhesus macaque IL-12 protein
>90%, by SDS-PAGE under reducing conditions and visualized by silver stain
<0.10 EU per 1 μg of the protein by the LAL method.
35.6 kDa (p40), 23.4 kDa (p35). Disclaimer note: The observed molecular weight of the protein may vary from the listed predicted molecular weight due to post translational modifications, post translation cleavages, relative charges, and other experimental factors.
Interleukin 12 (IL-12) is a 70 - 75 kDa heterodimeric glycoprotein that belongs to the IL-12 family of cytokines (1 - 3). Monkey IL-12 consists of two disulfide-linked subunits which are 35 kDa and 40 kDa in size. They show no meaningful amino acid (aa) similarity (4). The mature 35 kDa subunit (p35; also IL-12A) is an alpha -helix, 197 aa in length, that contains seven cysteines and two potential N-linked glycosylation sites (4). Mature Rhesus monkey p35 is 94%, 98%, 97%, 57%, 81%, and 82% aa identical to human, mangabey, baboon, mouse, equine and porcine mature p35, respectively. The mature 40 kDa subunit (p40; alsoIL-12B) is 306 aa in length and contains one intrachain disulfide bond plus three potential N-linked glycosylation sites. Mature Rhesus p40 is 96%, 97%, 99%, 67%, 85%, and 80% aa identical to human, mangabey, baboon, mouse, equine, and porcine p40, respectively. While p35 is reminescent of a hematopoietin ligand, p40 strongly resembles the N-terminus of a hematopoietin receptor, exhibiting a WSXWS motif, an immunoglobulin-like domain, and one fibronectin type III domain (5). This has led to the suggestion that IL-12 may be a cytokine-receptor analog to the IL-6/soluble IL-6R complex (6 - 8). Notably, while p40 may circulate as a monomer or homodimer, p35 is never found by itself. Cells known to produce IL-12 include macrophages and dendritic cells, monocytes, Langerhans cells, neutrophils, and keratinocytes. Functionally, IL-12 has been shown to both enhance cytotoxic activity and induce interferon-gamma (IFN-gamma ) production in NK cells and T cells. In response to infection, IL-27 is released initially, promoting a Th0 to Th0/1 transition state. IL-12 follows next, generating Th1 effector cells. With IL-18, IL-12 creates Th1 memory cells out of effector cells (1 - 3, 6, 7).
Hunter, C.A. (2005) Nat. Rev. Immunol. 5:521.
Langrish, C.L. et al. (2004) Immunol. Rev. 202:96.
Kreymborg, K. et al. (2005) Expert Opin. Ther. Targets 9:1123.
Villinger, F. et al. (1995) J. Immunol. 155:3946.
GenBank Accession # P48095.
Brombacher, F. et al. (2003) Trends Immunol. 24:207.
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