Gene/Protein
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Enzyme
Compound
Pivot Concepts:
Gene/Protein
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Target Concepts:
Gene/Protein
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Query: EC:2.7.11.25 (
MEKK1
)
1,856
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Transforming growth factor beta (TGF-beta)-activated kinase (TAK1) is known for its involvement in TGF-beta signaling and its ability to activate the p38-mitogen-activated protein kinase (MAPK) pathway. This report shows that TAK1 is also a strong activator of c-Jun N-terminal kinase (JNK). Both the wild-type and a constitutively active mutant of TAK1 stimulated JNK in transient transfection assays.
Mitogen-activated protein kinase kinase 4
(
MKK4
)/stress-activated protein kinase/extracellular signal-regulated kinase (SEK1), a dual-specificity kinase that phosphorylates and activates JNK, synergized with TAK1 in activating JNK. Conversely, a dominant-negative (
MKK4
/SEK1 mutant inhibited TAK1-induced JNK activation. A kinasedefective mutant of TAK1 effectively suppressed hematopoietic progenitor kinase-1 (HPK1)-induced JNK activity but had little effect on germinal center kinase activation of JNK. There are two additional MAPK kinase kinases,
MEKK1
and mixed lineage kinase 3 (MLK3), that are also downstream of HPK1 and upstream of
MKK4
/SEK mutant. However, because the dominant-negative mutants of
MEKK1
and MLK3 did not inhibit TAK1-induced JNK activity, we conclude that activation of JNK1 by TAK1 is independent of
MEKK1
and MLK3. In addition to TAK1, TGF-beta also stimulated JNK activity. Taken together, these results identify TAK1 as a regulator in the HPK1 --> TAK1 -->
MKK4
/SEK1 --> JNK kinase cascade and indicate the involvement of JNK in the TGF-beta signaling pathway. Our results also suggest the potential roles of TAK1 not only in the TGF-beta pathway but also in the other HPK1/JNK1-mediated pathways.
...
PMID:Activation of the hematopoietic progenitor kinase-1 (HPK1)-dependent, stress-activated c-Jun N-terminal kinase (JNK) pathway by transforming growth factor beta (TGF-beta)-activated kinase (TAK1), a kinase mediator of TGF beta signal transduction. 927 37
