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:2.7.11.25 (
MEKK1
)
1,856
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Protein kinase C-associated kinase (
PKK
, also known as
RIP4
/
DIK
) activates NFkappaB when overexpressed in cell lines and is required for keratinocyte differentiation in vivo. However, very little is understood about the factors upstream of
PKK
or how
PKK
activates NFkappaB. Here we show that certain catalytically inactive mutants of
PKK
can activate NFkappaB, although to a lesser degree than wild type
PKK
. The deletion of specific domains of wild type
PKK
diminishes the ability of this enzyme to activate NFkappaB; the same deletions made on a catalytically inactive
PKK
background completely ablate NFkappaB activation.
PKK
may be phosphorylated by two specific mitogen-activated protein kinase kinase kinases,
MEKK2
and
MEKK3
, and this interaction may in part be mediated through a critical activation loop residue, Thr184. Catalytically inactive
PKK
mutants that block phorbol ester-induced NFkappaB activation do not interfere with, but unexpectedly enhance, the activation of NFkappaB by these two mitogen-activated protein kinase kinase kinases. Taken together, these data indicate that
PKK
may function in both a kinase-dependent as well as a kinase-independent manner to activate NFkappaB.
...
PMID:Protein kinase C-associated kinase can activate NFkappaB in both a kinase-dependent and a kinase-independent manner. 1267 34
