The PHD motif of Map3k1 activates cytokine-dependent MAPK signaling.
We generated a mutation in the gene encoding mitogen-activated protein kinase kinase kinase 1 (Map3k1) that results in a protein with an inactive plant homeodomain (PHD). Map3k1(mPHD) cells are defective in cytokine-mediated MAPK signaling. Protein array identified transforming growth factor (TGF-β)-activated kinase 1 binding protein 1 (Tab1) as a PHD substrate. The Map3k1 PHD transfers Lys63-linked poly-ubiquitin onto Tab1 to activate MAPKs.
Department of Medicine; Imperial College London ; London, U.K.
Ewen
E
Gallagher
Department of Medicine; Imperial College London ; London, U.K.
Tesha
T
Suddason
differentiation; signaling; stem cell; tumorigenesis; ubiquitin