Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:2.7.11.24 (
mitogen-activated protein kinase
)
95,810
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Receptor expressed in lymphoid tissues
(
RELT
) is a new member of the TNFR family with little known regarding its signaling. Typically, TNFRs engage TRAFs for activation of NF-kappaB and
MAPK
cascades. We found that
RELT
does not use the standard signaling pathways characteristic of other TNFRs. While overexpression of
RELT
in 293 cells induced p38 and
JNK
activation, it did not activate NF-kappaB. In addition, no binding of
RELT
to TRAF1,2,3,5, or 6 was detected. Using a yeast two-hybrid system, we identified a Ste20-related proline-alanine-rich kinase (SPAK) that binds
RELT
. Disruption of the SPAK binding motif, 349RFRV, in
RELT
inhibited
RELT
activation of p38 and
JNK
. In addition, a kinase-dead SPAK acted as an inhibitor of
RELT
signaling. Thus, we conclude that
RELT
does not rely on the canonical TRAF pathways for its function, but instead uses a kinase, SPAK, to mediate p38 and
JNK
activation.
...
PMID:The TNF receptor, RELT, binds SPAK and uses it to mediate p38 and JNK activation. 1653 Jul 27
