Activation of Stress-activated Protein Kinases/c-Jun N-terminal Protein Kinases (SAPKs/JNKs) by a Novel Mitogen-activated Protein Kinase Kinase (MKK7)

Mitogen-activated protein kinase (MAPK) kinases (MKKs) are dual-specificity protein kinases that phosphorylate and activate MAPK. We have isolated a cDNA encoding a novel protein kinase that has significant homology to MKKs. The novel kinase MKK7 has a nucleotide sequence that encodes an open readin...

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Bibliographic Details
Published in:	The Journal of biological chemistry Vol. 272; no. 51; pp. 32378 - 32383
Main Authors:	Yao, Zhengbin, Diener, Katrina, Wang, Xuhong Sunny, Zukowski, Mark, Matsumoto, Goichi, Zhou, Guisheng, Mo, Rong, Sasaki, Takehiko, Nishina, Hiroshi, Hui, Chi Chung, Tan, Tse-Hua, Woodgett, James P., Penninger, Josef M.
Format:	Journal Article
Language:	English
Published:	United States Elsevier Inc 19-12-1997 American Society for Biochemistry and Molecular Biology
Subjects:	Amino Acid Sequence Animals Base Sequence Calcium-Calmodulin-Dependent Protein Kinases - metabolism Cloning, Molecular Enzyme Activation Humans JNK Mitogen-Activated Protein Kinases MAP Kinase Kinase 7 Mice Mitogen-Activated Protein Kinase Kinases Mitogen-Activated Protein Kinases Molecular Sequence Data Mutagenesis Open Reading Frames Protein Kinases - genetics Protein Kinases - metabolism RNA, Messenger - genetics Sequence Homology, Amino Acid
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Summary:	Mitogen-activated protein kinase (MAPK) kinases (MKKs) are dual-specificity protein kinases that phosphorylate and activate MAPK. We have isolated a cDNA encoding a novel protein kinase that has significant homology to MKKs. The novel kinase MKK7 has a nucleotide sequence that encodes an open reading frame of 347 amino acids with 11 kinase subdomains. MKK7 is ubiquitously expressed in all adult and embryonic organs but displays high expression in epithelial tissues at later stages of fetal development. When transiently expressed in 293 cells, MKK7 specifically activated stress-activated protein kinases (SAPKs)/c-Jun N-terminal protein kinases (JNKs) but not extracellular-regulated kinase or p38 kinase. A kinase-negative mutant of MKK7 inhibits interleukin-1β, lipopolysaccharide, and MEKK1-induced SAPK/JNK activation. Thus, MKK7 is a new member of the MAPK kinase family that functions upstream of SAPK/JNK in the SAPK/JNK signaling pathway.
ISSN:	0021-9258 1083-351X
DOI:	10.1074/jbc.272.51.32378