PMID- 17698565
OWN - NLM
STAT- MEDLINE
DCOM- 20080125
LR  - 20240109
IS  - 0953-8178 (Print)
IS  - 0953-8178 (Linking)
VI  - 19
IP  - 8
DP  - 2007 Aug
TI  - Expression and function of mixed lineage kinases in dendritic cells.
PG  - 923-33
AB  - Dendritic cells (DCs) sense the presence of conserved microbial structures in 
      their local microenvironment via specific pattern recognition receptors (PRRs). 
      This leads to a programme of changes, which include migration and activation, and 
      enables them to induce adaptive T cell immunity. Mitogen-activated protein 
      kinases (MAPKs) are implicated in this response, but the pathways leading from 
      PRR ligation to MAPK activation, and hence DC activation, are not fully 
      understood. Recent studies in the nervous system have suggested that the mixed 
      lineage kinase (MLK) family of MAPK kinase kinase proteins may be involved as an 
      intermediary step between PRRs and MAPKs. Therefore, in this study, we have used 
      a well-established DC model to explore the role of MLKs in these cells. Messenger 
      RNA for MLKs 2, 3, 4 and DLK and protein for MLKs 2, 3 and DLK are found in DC. 
      DC activation in response to model PRR ligands, such as LPS or poly (I:C), is 
      accompanied by phosphorylation of MLK3. In contrast, another known PRR ligand, 
      zymosan, induces little MLK3 phosphorylation. Inhibition of MLK activity using a 
      pharmacological inhibitor, CEP11004, blocks p38 and Jun N-terminal kinase (JNK) 
      MAPK activation in response to LPS and poly (I:C), but not zymosan. The 
      inhibition is associated with a block in DC activation as measured by 
      cell-surface marker expression and cytokine secretion. Thus, MLKs are expressed 
      in DC, and are implicated in DC activation, and the involvement of MLKs appears 
      to be selective, depending on the nature of the DC stimulus.
FAU - Handley, Matthew E
AU  - Handley ME
AD  - Department of Immunology and Molecular Pathology, University College London, 
      Windeyer Institute, 46 Cleveland Street, London W1T 4JF, UK.
FAU - Rasaiyaah, Jane
AU  - Rasaiyaah J
FAU - Barnett, James
AU  - Barnett J
FAU - Thakker, Manish
AU  - Thakker M
FAU - Pollara, Gabriele
AU  - Pollara G
FAU - Katz, David R
AU  - Katz DR
FAU - Chain, Benjamin M
AU  - Chain BM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070813
PL  - England
TA  - Int Immunol
JT  - International immunology
JID - 8916182
RN  - 0 (Anthracenes)
RN  - 0 (CEP-11004)
RN  - 0 (Carbazoles)
RN  - 0 (Imidazoles)
RN  - 0 (Indoles)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Pyridines)
RN  - 0 (Toll-Like Receptors)
RN  - 1TW30Y2766 (pyrazolanthrone)
RN  - 9010-72-4 (Zymosan)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.25 (MAP Kinase Kinase Kinases)
RN  - OU13V1EYWQ (SB 203580)
SB  - IM
MH  - Anthracenes/pharmacology
MH  - Antigen Presentation
MH  - Carbazoles/pharmacology
MH  - Dendritic Cells/*enzymology/immunology/metabolism
MH  - Humans
MH  - Imidazoles/pharmacology
MH  - Indoles/pharmacology
MH  - Lipopolysaccharides/immunology
MH  - MAP Kinase Kinase Kinases/antagonists & inhibitors/*metabolism
MH  - MAP Kinase Signaling System
MH  - Mitogen-Activated Protein Kinases/antagonists & inhibitors/*metabolism
MH  - Phosphorylation/drug effects
MH  - Pyridines/pharmacology
MH  - Toll-Like Receptors/*metabolism
MH  - Zymosan/immunology
MH  - p38 Mitogen-Activated Protein Kinases/antagonists & inhibitors/*metabolism
EDAT- 2007/08/19 09:00
MHDA- 2008/01/26 09:00
CRDT- 2007/08/19 09:00
PHST- 2007/08/19 09:00 [pubmed]
PHST- 2008/01/26 09:00 [medline]
PHST- 2007/08/19 09:00 [entrez]
AID - dxm050 [pii]
AID - 10.1093/intimm/dxm050 [doi]
PST - ppublish
SO  - Int Immunol. 2007 Aug;19(8):923-33. doi: 10.1093/intimm/dxm050. Epub 2007 Aug 13.