Molecular cloning and characterization of human JNKK2, a novel Jun NH2-terminal kinase-specific kinase.
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.
Wu
Z
Z
Department of Pharmacology, University of California, San Diego, La Jolla 92093-0636, USA.
Wu
J
J
Jacinto
E
E
Karin
M
M
D000595:Amino Acid Sequence; D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002460:Cell Line; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D004330:Drosophila / Q000201:enzymology / Q000235:genetics; D004789:Enzyme Activation; D015870:Gene Expression; D006367:HeLa Cells; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D048688:MAP Kinase Kinase 7; D020929:Mitogen-Activated Protein Kinase Kinases; D020928:Mitogen-Activated Protein Kinases; D008969:Molecular Sequence Data; D011494:Protein Kinases / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity
D018076:DNA, Complementary; D012333:RNA, Messenger; D011494:Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D048688:MAP Kinase Kinase 7; C482569:MAP2K7 protein, human; D020929:Mitogen-Activated Protein Kinase Kinases