Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\27402796
.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Biochem+J
2016 ; 473
(18
): 2845-61
Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
TLR and TNF-R1 activation of the MKK3/MKK6-p38? axis in macrophages is mediated
by TPL-2 kinase
#MMPMID27402796
Pattison MJ
; Mitchell O
; Flynn HR
; Chen CS
; Yang HT
; Ben-Addi H
; Boeing S
; Snijders AP
; Ley SC
Biochem J
2016[Sep]; 473
(18
): 2845-61
PMID27402796
show ga
Previous studies suggested that Toll-like receptor (TLR) stimulation of the p38?
MAP kinase (MAPK) is mediated by transforming growth factor-?-activated kinase 1
(TAK1) activation of MAPK kinases, MKK3, MKK4 and MKK6. We used quantitative mass
spectrometry to monitor tumour progression locus 2 (TPL-2)-dependent protein
phosphorylation following TLR4 stimulation with lipopolysaccharide, comparing
macrophages from wild-type mice and Map3k8(D270A/D270A) mice expressing
catalytically inactive TPL-2 (MAP3K8). In addition to the established TPL-2
substrates MKK1/2, TPL-2 kinase activity was required to phosphorylate the
activation loops of MKK3/6, but not of MKK4. MKK3/6 activation required I?B
kinase (IKK) phosphorylation of the TPL-2 binding partner nuclear factor
?-light-chain-enhancer of activated B cells (NF-?B1) p105, similar to MKK1/2
activation. Tumour necrosis factor (TNF) stimulation of MKK3/6 phosphorylation
was similarly dependent on TPL-2 catalytic activity and IKK phosphorylation of
NF-?B1 p105. Owing to redundancy of MKK3/6 with MKK4, Map3k8(D270A) mutation only
fractionally decreased lipopolysaccharide activation of p38?. TNF activation of
p38?, which is mediated predominantly via MKK3/6, was substantially reduced.
TPL-2 catalytic activity was also required for MKK3/6 and p38? activation
following macrophage stimulation with Mycobacterium tuberculosis and Listeria
monocytogenes Our experiments demonstrate that the IKK/NF-?B1 p105/TPL-2
signalling pathway, downstream of TAK1, regulates MKK3/6 and p38? activation in
macrophages in inflammation.
|Animals
[MESH]
|Enzyme Activation
[MESH]
|Macrophages/*enzymology
[MESH]
|Mass Spectrometry
[MESH]
|Mice
[MESH]
|Protein Kinases/*metabolism
[MESH]
|Receptors, Tumor Necrosis Factor, Type I/*metabolism
[MESH]
free
free
free
