Identification of a dual specificity kinase that activates the Jun kinases and p38-Mpk2.
One Ras-dependent protein kinase cascade leading from growth factor receptors to the ERK (extracellular signal-regulated kinases) subgroup of mitogen-activated protein kinases (MAPKs) is dependent on the protein kinase Raf-1, which activates the MEK (MAPK or ERK kinase) dual specificity kinases. A second protein kinase cascade leading to activation of the Jun kinases (JNKs) is dependent on MEKK (MEK kinase). A dual-specificity kinase that activates JNK, named JNKK, was identified that functions between MEKK and JNK. JNKK activated the JNKs but did not activate the ERKs and was unresponsive to Raf-1 in transfected HeLa cells. JNKK also activated another MAPK, p38 (Mpk2; the mammalian homolog of HOG1 from yeast), whose activity is regulated similarly to that of the JNKs.
Lin
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A
Department of Pharmacology, University of California-San Diego School of Medicine, La Jolla 92093-0636, USA.
Minden
A
A
Martinetto
H
H
Claret
F X
FX
Lange-Carter
C
C
Mercurio
F
F
Johnson
G L
GL
Karin
M
M
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002460:Cell Line; D004789:Enzyme Activation; D004815:Epidermal Growth Factor / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D048728:MAP Kinase Kinase Kinase 1; D020929:Mitogen-Activated Protein Kinase Kinases; D020928:Mitogen-Activated Protein Kinases; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011494:Protein Kinases / Q000737:chemistry / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019908:Proto-Oncogene Proteins c-raf; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013379:Substrate Specificity; D014162:Transfection; D048051:p38 Mitogen-Activated Protein Kinases
D011518:Proto-Oncogene Proteins; D011993:Recombinant Fusion Proteins; D004815:Epidermal Growth Factor; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D019908:Proto-Oncogene Proteins c-raf; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D048728:MAP Kinase Kinase Kinase 1; C482576:MAP3K1 protein, human; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases