| First Author | MacNeil AJ | Year | 2014 |
| Journal | J Leukoc Biol | Volume | 95 |
| Issue | 6 | Pages | 903-15 |
| PubMed ID | 24453276 | Mgi Jnum | J:211932 |
| Mgi Id | MGI:5576994 | Doi | 10.1189/jlb.0713401 |
| Citation | MacNeil AJ, et al. (2014) Stem cell factor induces AP-1-dependent mast cell IL-6 production via MAPK kinase 3 activity. J Leukoc Biol 95(6):903-15 |
| abstractText | Mast cells are critical immune effectors abundant in tissues interfacing with the environment and have major roles in allergen-induced inflammation and host responses to infection. SCF is a regulator of mast cell function and growth. However, the critical mechanisms in SCF-directed events remain incompletely defined. Here, we have investigated the role of MKK3 in mast cell SCF signaling-dependent functions by using BMMCs from MKK3-deficient mice. MKK3 was phosphorylated rapidly and persistently following SCF-induced activation and contributed to mast cell proliferation but not survival or migration in response to SCF. Analysis of SCF-induced mast cell mediator secretion demonstrated that IL-6 production is specifically dependent on MKK3 signals, both independently and in concert with IgE. Analysis of SCF-induced signaling showed that sustained p38 phosphorylation was impaired in MKK3-deficient mast cells, where as early JNK and IkappaBalpha activation were enhanced. Notably, SCF-inducible expression and activation of c-Jun, a component of the AP-1 transcription factor, was significantly dependent on MKK3. Accordingly, AP-1 DNA-binding activity and interaction with the IL6 gene promoter was markedly impaired in MKK3-deficient mast cells, whereas transcription factors of the Egr family, NF-kappaB, and NFAT retained near-full activity. These results designate MKK3 as a novel, positive regulator of SCF-induced mast cell proliferation and a critical signaling protein for AP-1-dependent IL-6 production. |
