| First Author | Funakoshi-Tago M | Year | 2005 |
| Journal | J Biochem | Volume | 137 |
| Issue | 2 | Pages | 189-97 |
| PubMed ID | 15749833 | Mgi Jnum | J:115430 |
| Mgi Id | MGI:3691709 | Doi | 10.1093/jb/mvi018 |
| Citation | Funakoshi-Tago M, et al. (2005) Functional role of c-Src in IL-1-induced NF-kappa B activation: c-Src is a component of the IKK complex. J Biochem 137(2):189-97 |
| abstractText | Interleukin-1 (IL-1) mediates numerous host responses through the rapid activation of nuclear factor-kappa B (NF-kappa B), but the signal pathways leading to NF-kappa B activation are regulated at multiple stages. Here, we propose a novel regulatory system for IL-1-induced NF-kappa B activation by a tyrosine kinase, c-Src. The kinase activity of c-Src increases in an IL-1-dependent manner and the ectopic expression of c-Src augments IL-1-induced NF-kappa B activation, suggesting the involvement of c-Src in IL-1 signaling. However, a Src family inhibitor, PP2 failed to inhibit IL-1-induced NF-kappa B activation, and the expression of a c-Src mutant lacking kinase activity (c-Src KD) augmented IL-1-induced NF-kappa B activation as well as wild type c-Src, indicating that the tyrosine kinase activity is not required for IL-1-induced NF-kappa B activation. Furthermore, a physiological interaction between c-Src and I kappa B kinase gamma (IKK gamma) was observed, implying the involvement of c-Src in the IKK-complex. While c-Src augmented IL-1-induced IKK activation independent of its kinase activity, the region comprising amino acids 361-440 in the c-Src kinase domain are required for NF-kappa B activation. The same region of c-Src is also required for IL-1-induced IKK activation and the association with IKK gamma. Taken together, our results suggest that c-Src plays a critical role in IL-1-induced NF-kappa B activation through the IKK complex. |
