Identification and characterization of functional domains in a mixed lineage kinase LZK.
The mixed lineage kinase (MLK) family is a recently described protein kinase family. The MLKs contain a kinase domain followed by a dual leucine zipper-like motif. We previously reported the molecular cloning of LZK (leucine zipper-bearing kinase), a novel MLK, and that LZK activated the c-Jun NH2 terminal kinase (JNK)/stress-activated protein kinase (SAPK) pathway through MKK7 in cells. Here, we reveal that LZK forms dimers/oligomers through its dual leucine zipper-like motif, and that this is necessary for activation of the JNK/SAPK pathway. We also identify the C-terminal functional region of LZK, which is indispensable for the activation of SEK1, but not that of MKK7.
Ikeda
A
A
Department of Biological Chemistry and CREST (Core Research for Educational Science and Technology) Project, Japan Science and Technology Corporation, Graduate School of Pharmaceutical Sciences, Kyoto University, 606-8501, Kyoto, Japan.
Masaki
M
M
Kozutsumi
Y
Y
Oka
S
S
Kawasaki
T
T
D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D019281:Dimerization; D004789:Enzyme Activation; D017353:Gene Deletion; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D016350:Leucine Zippers; D048670:MAP Kinase Kinase 4; D048688:MAP Kinase Kinase 7; D020930:MAP Kinase Kinase Kinases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D020929:Mitogen-Activated Protein Kinase Kinases / Q000235:genetics / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D011233:Precipitin Tests; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection
D011993:Recombinant Fusion Proteins; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D020930:MAP Kinase Kinase Kinases; C109162:MAP3K13 protein, human; D048670:MAP Kinase Kinase 4; D048688:MAP Kinase Kinase 7; C482559:MAP2K4 protein, human; C482569:MAP2K7 protein, human; D020929:Mitogen-Activated Protein Kinase Kinases