| First Author | Zou JJ | Year | 1995 |
| Journal | J Biol Chem | Volume | 270 |
| Issue | 11 | Pages | 5864-71 |
| PubMed ID | 7890716 | Mgi Jnum | J:23768 |
| Mgi Id | MGI:71457 | Doi | 10.1074/jbc.270.11.5864 |
| Citation | Zou JJ, et al. (1995) Structure-function analysis of the p35 subunit of mouse interleukin 12. J Biol Chem 270(11):5864-71 |
| abstractText | Mouse IL-12 acts on both mouse and human cells; human IL-12 acts only on human cells. This species specificity is determined by the p35 subunit of the IL-12 heterodimer. Since mouse and human p35 sequences are 60% identical, the determinants for the species specificity most likely residue in the nonhomologous sequences of mouse p35. To identify the regions on the p35 subunit interacting with the mouse IL-12 receptor, we constructed a series of chimeric mouse-human p35 molecules by replacing mouse sequences with the nonhomologous human counterparts. An IL-12 heterodimer containing a mouse-human p35 chimera with five residues changed in three discontinuous sites had drastically reduced (750-3000-fold) bioactivities on mouse cells. However, the competitive binding activity of the same mutant IL-12 heterodimer on mouse cells was only reduced 30-fold relative to wild-type IL-12. These findings therefore suggest that 1) the mouse p35 subunit participates in both receptor binding and signaling, 2) the mutations introduced into p35 affect signaling to a much greater extent than receptor binding, and 3) the five residues identified on p35 are required for interacting with the mouse, but not with the human IL-12 receptor and as such contribute extensively to the observed species specificity of IL-12. |
