Article ID Journal Published Year Pages File Type
2833337 Molecular Immunology 2007 8 Pages PDF
Abstract
Cot is a serine/threonine protein kinase and is classified as a mitogen-activated protein (MAP) kinase kinase kinase. Overexpression of this protein has been shown to activate the extracellular signal-regulated kinase, the c-Jun N-terminal kinase, and the p38 MAP kinase pathways and to stimulate NF-AT and NF-κB-dependent transcription. Here we have shown that Cot kinase activity is intimately involved in the high affinity receptor for IgE (FcɛRI)-mediated nuclear translocation of NF-κB1 independent of NF-κB-inducing kinase (NIK) in rat basophilic leukemia (RBL-2H3) cells. A transfected green fluorescent protein-tagged NF-κB1 (GFP-NF-κB1) resided in the cytoplasm in RBL-2H3 cells and it remained in the cytoplasm even when Cot tagged with red fluorescent protein (Cot-RFP) was co-expressed. Western blotting analysis showed that IκB kinases (IKKs) were expressed in RBL-2H3 cells but NIK was not. GFP-NF-κB1 translocated from the cytoplasm to the nucleus after the aggregation of FcɛRI in Cot-transfected cells but not in kinase-deficient Cot-transfected cells. This finding gives a new insight into the role of Cot in the FcɛRI-mediated NF-κB activation in mast cells.
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Life Sciences Biochemistry, Genetics and Molecular Biology Molecular Biology
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