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PMID: 9372971 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Molecular cloning and characterization of human JNKK2, a novel Jun NH2-terminal kinase-specific kinase.

Molecular and cellular biology ·Vol. 17 ·No. 12 ·1997-12-00 ·Pages 7407-16

Wu Z, Wu J, Jacinto E, Karin M

Abstract

At least three mitogen-activated protein kinase (MAPK) cascades were identified in mammals, each consisting of a well-defined three-kinase module composed of a MAPK, a MAPK kinase (MAPKK), and a MAPKK kinase (MAPKKK). These cascades play key roles in relaying various physiological, environmental, or pathological signals from the environment to the transcriptional machinery in the nucleus. One of these MAPKs, c-Jun N-terminal kinase (JNK), stimulates the transcriptional activity of c-Jun in response to growth factors, proinflammatory cytokines, and certain environmental stresses, such as short wavelength UV light or osmotic shock. The JNKs are directly activated by the MAPKK JNKK1/SEK1/MKK4. However, inactivation of the gene encoding this MAPKK by homologous recombination suggested the existence of at least one more JNK-activating kinase. Recently, the JNK cascade was found to be structurally and functionally conserved in Drosophila, where DJNK is activated by the MAPKK DJNKK (hep). By a database search, we identified an expressed sequence tag (EST) encoding a portion of human MAPKK that is highly related to DJNKK (hep). We used this EST to isolate a full-length cDNA clone encoding a human JNKK2. We show that JNKK2 is a highly specific JNK kinase. Unlike JNKK1, it does not activate the related MAPK, p38. Although the regulation of JNKK1 activities and that of JNKK2 activities could be very similar, the two kinases may play somewhat different regulatory roles in a cell-type-dependent manner.

MeSH Terms
Amino Acid Sequence Animals Calcium-Calmodulin-Dependent Protein Kinases/metabolism Cell Line Cloning, Molecular DNA, Complementary/genetics Drosophila/enzymology,genetics Enzyme Activation Gene Expression HeLa Cells Humans JNK Mitogen-Activated Protein Kinases MAP Kinase Kinase 4 MAP Kinase Kinase 7 Mitogen-Activated Protein Kinase Kinases Mitogen-Activated Protein Kinases Molecular Sequence Data Protein Kinases/genetics,metabolism RNA, Messenger/genetics,metabolism Sequence Homology, Amino Acid Substrate Specificity
Chemicals
DNA, Complementary RNA, Messenger Protein Kinases Calcium-Calmodulin-Dependent Protein Kinases JNK Mitogen-Activated Protein Kinases Mitogen-Activated Protein Kinases MAP Kinase Kinase 4 MAP Kinase Kinase 7 MAP2K7 protein, human Mitogen-Activated Protein Kinase Kinases
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Wu Z
Department of Pharmacology, University of California, San Diego, La Jolla 92093-0636, USA.
Wu J
Jacinto E
Karin M
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.17.12.7407
Published
1997-12-00
Pages
7407-16
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC232596
Subset
IM
Grants
NIEHS NIH HHS · ES04151 · United States
Databases
GENBANK
AF014401
External Links
PubMed source DOI: 10.1128/MCB.17.12.7407 PMC Full Text View journal details
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