PMID- 12093796
OWN - NLM
STAT- MEDLINE
DCOM- 20021029
LR  - 20210206
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 277
IP  - 36
DP  - 2002 Sep 6
TI  - The serine protease plasmin triggers expression of MCP-1 and CD40 in human 
      primary monocytes via activation of p38 MAPK and janus kinase (JAK)/STAT 
      signaling pathways.
PG  - 33509-17
AB  - The mechanism of proinflammatory activation of human monocytes by plasmin is 
      unknown. Here we demonstrate that in human primary monocytes, plasmin stimulates 
      mitogen-activated protein kinase (MAPK) signaling via phosphorylation of MAPK 
      kinase 3/6 (MKK3/6) and p38 MAPK that triggers subsequent DNA binding of 
      transcription factor activator protein-1 (AP-1). The AP-1 complex contained 
      phosphorylated c-Jun and ATF2, and its DNA binding activity was blocked by the 
      p38 MAPK inhibitor SB203580. In addition, plasmin elicits Janus kinase 
      (JAK)/signal transducer and activator of transcription (STAT) signaling, as 
      detected by phosphorylation of JAK1 tyrosine kinase and STAT1 and STAT3 proteins. 
      Plasmin-induced DNA binding of STAT1 and STAT3 was blocked by SB203580 and AG490, 
      inhibitors of p38 MAPK and JAK, respectively, but not by U0126, an inhibitor of 
      MKK1/2. DNA binding of NF-kappaB remained unaffected by any of these inhibitors. 
      The plasmin-induced signaling led to expression of monocyte chemoattractant 
      protein-1 (MCP-1) and CD40, which required activation of both p38 MAPK and 
      JAK/STAT signaling pathways. Additionally, signaling through both p38 MAPK and 
      JAK is involved in the plasmin-mediated monocyte migration, whereas the 
      formylmethionylleucylphenylalanine-induced chemotaxis remained unaffected. Taken 
      together, our data demonstrate a novel function of the serine protease plasmin in 
      a proinflammatory signaling network.
FAU - Burysek, Ladislav
AU  - Burysek L
AD  - Department of Pharmacology of Natural Products and Clinical Pharmacology, 
      University of Ulm, D-89081 Ulm, Germany.
FAU - Syrovets, Tatiana
AU  - Syrovets T
FAU - Simmet, Thomas
AU  - Simmet T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20020701
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (CD40 Antigens)
RN  - 0 (Chemokine CCL2)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (NF-kappa B)
RN  - 0 (STAT1 Transcription Factor)
RN  - 0 (STAT1 protein, human)
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (STAT3 protein, human)
RN  - 0 (Trans-Activators)
RN  - 42HK56048U (Tyrosine)
RN  - 452VLY9402 (Serine)
RN  - 9007-49-2 (DNA)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.2 (JAK1 protein, human)
RN  - EC 2.7.10.2 (Janus Kinase 1)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - EC 3.4.21.- (Serine Endopeptidases)
RN  - EC 3.4.21.7 (Fibrinolysin)
SB  - IM
MH  - Blotting, Western
MH  - CD40 Antigens/*biosynthesis/genetics
MH  - Cell Movement
MH  - Cells, Cultured
MH  - Chemokine CCL2/*biosynthesis/genetics
MH  - DNA/metabolism
MH  - DNA-Binding Proteins/metabolism
MH  - Dose-Response Relationship, Drug
MH  - Enzyme Activation
MH  - Fibrinolysin/*pharmacology
MH  - Humans
MH  - Janus Kinase 1
MH  - Mitogen-Activated Protein Kinases/metabolism
MH  - Monocytes/enzymology/*metabolism
MH  - NF-kappa B/metabolism
MH  - Phosphorylation
MH  - Precipitin Tests
MH  - Protein Binding
MH  - Protein Kinases/*metabolism
MH  - Protein-Tyrosine Kinases/metabolism
MH  - STAT1 Transcription Factor
MH  - STAT3 Transcription Factor
MH  - Serine/metabolism
MH  - Serine Endopeptidases/metabolism
MH  - Signal Transduction
MH  - Time Factors
MH  - Trans-Activators/*metabolism
MH  - Transcriptional Activation
MH  - Tyrosine/metabolism
MH  - p38 Mitogen-Activated Protein Kinases
EDAT- 2002/07/03 10:00
MHDA- 2002/10/31 04:00
CRDT- 2002/07/03 10:00
PHST- 2002/07/03 10:00 [pubmed]
PHST- 2002/10/31 04:00 [medline]
PHST- 2002/07/03 10:00 [entrez]
AID - S0021-9258(20)74512-6 [pii]
AID - 10.1074/jbc.M201941200 [doi]
PST - ppublish
SO  - J Biol Chem. 2002 Sep 6;277(36):33509-17. doi: 10.1074/jbc.M201941200. Epub 2002 
      Jul 1.