Cloning of DPK, a novel dendritic cell-derived protein kinase activating the ERK1/ERK2 and JNK/SAPK pathways

Mitogen-activated protein kinase (MAPK) cascades are the major signaling sy stems transducing extracellular signals into intracellular responses, which mainly include the extracellular signal-regulated kinase (ERK) pathway, th e c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK) pathwa y, and the p38 pathway. From dendritic cell cDNA library, we isolated a ful l-length cDNA encoding a potentially novel 898-residue kinase, which was de signated DPK. The protein contained a potential kinase domain at the N-term inal exhibiting homology with MEKK1-, MEKK2-, MEKK3-, MEKK4-, MEKK5-, Tp1-2 -, and p21-activated kinases (PAKs), but no GTPase-binding domain which is characteristic of PAHs. Northern blotting analysis showed that DPK was ubiq uitously expressed in normal tissues, with abundant expression in kidney, s keletal muscle, heart, and liver. When overexpressed in transfected NIH3T3 cells, it could activate both the ERK1/ERK2 pathway and the SAPK pathway in a dose-dependent manner, but not affect the p38 pathway. These findings su ggested that DPK might be a novel candidate MAPKKK. (C) 2000 Academic Press .