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 systems transducing extracellular signals into intracellular responses, which mainly include the extracellular signal-regulated kinase (ERK) pathway, the c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK) pathway, and the p38 pathway. From dendritic cell cDNA library, we isolated a full-length cDNA encoding a potentially novel 898-residue kinase, which was designated DPK. The protein contained a potential kinase domain at the N-terminal exhibiting homology with MEKK1-, MEKK2-, MEKK3-, MEKK4-, MEKK5-, Tpl-2-, and p21-activated kinases (PAKs), but no GTPase-binding domain which is characteristic of PAKs. Northern blotting analysis showed that DPK was ubiquitously expressed in normal tissues, with abundant expression in kidney, skeletal 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 suggested that DPK might be a novel candidate MAPKKK.
Department of Immunology, Second Military Medical University, 800 Xiangyin Road, Shanghai, 200433, People's Republic of China.
W
W
Zhang
T
T
Chen
T
T
Wan
L
L
He
N
N
Li
Z
Z
Yuan
X
X
Cao
D000595:Amino Acid Sequence; D003001:Cloning, Molecular; D003713:Dendritic Cells / Q000502:physiology*; D004789:Enzyme Activation; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020930:MAP Kinase Kinase Kinases / Q000235:genetics* / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000235:genetics*; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020929:Mitogen-Activated Protein Kinase Kinases / Q000235:genetics / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D011494:Protein Kinases / Q000235:genetics* / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases; D016415:Sequence Alignment; D015398:Signal Transduction; D000099317:Hippo Kinases
D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020930:MAP Kinase Kinase Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020929:Mitogen-Activated Protein Kinase Kinases; D020928:Mitogen-Activated Protein Kinases; D009419:Nerve Tissue Proteins; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; C109163:STK24 protein, human; D000099317:Hippo Kinases