A novel kinase cascade mediated by mitogen-activated protein kinase kinase 6 and MKK3.
A cDNA encoding a novel member of the mitogen-activated protein kinase kinase (MAPKK) family, MAPKK6, was isolated and found to encode a protein of 334 amino acids, with a calculated molecular mass of 37 kDa that is 79% identical to MKK3. MAPKK6 was shown to phosphorylate and specifically activate the p38/MPK2 subgroup of the mitogen-activated protein kinase superfamily and could be demonstrated to be phosphorylated and activated in vitro by TAK1, a recently identified MAPKK kinase. MKK3 was also shown to be a good substrate for TAK1 in vitro. Furthermore, when co-expressed with TAK1 in cells in culture, both MAPKK6 and MKK3 were strongly activated. In addition, co-expression of TAK1 and p38/MPK2 in cells resulted in activation of p38/MPK2. These results indicate the existence of a novel kinase cascade consisting of TAK1, MAPKK6/MKK3, and p38/MPK2.
Moriguchi
T
T
Department of Genetics and Molecular Biology, Institute for Virus Research, Kyoto University, Sakyo-ku, Kyoto 606-01, Japan.
Kuroyanagi
N
N
Yamaguchi
K
K
Gotoh
Y
Y
Irie
K
K
Kano
T
T
Shirakabe
K
K
Muro
Y
Y
Shibuya
H
H
Matsumoto
K
K
Nishida
E
E
Hagiwara
M
M
D000595:Amino Acid Sequence; D000818:Animals; D001323:Autoantibodies / Q000097:blood; D001483:Base Sequence; D001528:Behcet Syndrome / Q000201:enzymology / Q000276:immunology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D002460:Cell Line; D015342:DNA Probes / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D004789:Enzyme Activation; D006367:HeLa Cells; D006801:Humans; D066298:In Vitro Techniques; D048371:MAP Kinase Kinase 3; D048669:MAP Kinase Kinase 6; D020929:Mitogen-Activated Protein Kinase Kinases; D008969:Molecular Sequence Data; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D013379:Substrate Specificity; D014162:Transfection
D001323:Autoantibodies; D015342:DNA Probes; D018076:DNA, Complementary; D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048371:MAP Kinase Kinase 3; D048669:MAP Kinase Kinase 6; C482530:MAP2K3 protein, human; C482566:MAP2K6 protein, human; D020929:Mitogen-Activated Protein Kinase Kinases