First Author | Zhou H | Year | 2004 |
Journal | J Immunol | Volume | 172 |
Issue | 4 | Pages | 2559-68 |
PubMed ID | 14764729 | Mgi Jnum | J:88064 |
Mgi Id | MGI:3029081 | Doi | 10.4049/jimmunol.172.4.2559 |
Citation | Zhou H, et al. (2004) Microtubule-associated serine/threonine kinase-205 kDa and Fcgamma receptor control IL-12 p40 synthesis and NF-kappaB activation. J Immunol 172(4):2559-68 |
abstractText | Stimulation of murine macrophages with LPS results in the coordinated activation of a set of proinflammatory cytokines and costimulatory molecules, including TNF-alpha, IL-6, IL-1, IL-8, IL-12, and CD80. Macrophage LPS-induced synthesis of IL-12 is inhibited following FcgammaR ligation; TNF-alpha secretion is unchanged. We report that microtubule-associated serine/threonine kinase-205 kDa (MAST205) is required for LPS-induced IL-12 synthesis. RNA interference-mediated suppression of MAST205 results in the inhibition of LPS-stimulated IL-12 promoter activity and IL-12 secretion, from both J774 cells and bone marrow-derived macrophages. Similarly, dominant-negative MAST205 mutants inhibit LPS-stimulated IL-12 synthesis and NF-kappaB activation, but do not affect IL-1 or TNF-alpha signaling. Finally, macrophage FcgammaR ligation regulates MAST205 by inducing the rapid ubiquitination and proteasomal degradation of the protein. |