Open AccessMicrotubule-Associated Serine/Threonine Kinase-205 kDa and Fcγ Receptor Control IL-12 p40 Synthesis and NF-κB Activation
Author(s) -
Hui Zhou,
Huabao Xiong,
Hongxing Li,
Scott E. Plevy,
Paul D. Walden,
Massimo Sassaroli,
Glenn D. Prestwich,
Jay C. Unkeless
Publication year - 2004
Publication title -
the journal of immunology/the journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.737
H-Index - 372
eISSN - 1550-6606
pISSN - 0022-1767
DOI - 10.4049/jimmunol.172.4.2559
Subject(s) - proinflammatory cytokine , cd80 , microbiology and biotechnology , secretion , chemistry , phosphorylation , tumor necrosis factor alpha , kinase , biology , inflammation , biochemistry , immunology , in vitro , cd40 , cytotoxic t cell
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.