PMID- 12349947
OWN - NLM
STAT- MEDLINE
DCOM- 20030318
LR  - 20191106
IS  - 1567-5769 (Print)
IS  - 1567-5769 (Linking)
VI  - 2
IP  - 8
DP  - 2002 Jul
TI  - Tyrosine phosphorylation-mediated signal transduction in MCP-1-induced macrophage 
      activation: role for receptor dimerization, focal adhesion protein complex and 
      JAK/STAT pathway.
PG  - 1095-107
AB  - Monocyte chemoattractant protein-1 (MCP-1) plays a crucial role in the 
      recruitment of monocytes/macrophages associated with several inflammatory 
      diseases and malignancies. The early signal transduction mechanism of macrophage 
      activation in response to in vitro MCP-1 treatment was investigated. The 
      treatment of murine peritoneal macrophages with MCP-1 resulted in a significant 
      enhancement in the tyrosine phosphorylation of cellular proteins, which peaked 
      within 2.5-5 min of MCP-1 treatment. The MCP-1-induced tyrosine phosphorylation 
      of cellular proteins involved the phosphorylation of non-receptor tyrosine 
      kinases Lyn, JAK2, cytoskeletal binding protein paxillin and downstream 
      transcription factors STAT3 and STAT5. Immunoflourescence microscopical studies 
      on MCP-1-treated macrophages showed the cellular localization of the 
      tyrosine-phosphorylated proteins and bundling of actin filaments at the focal 
      adhesion points. MCP-1-induced association of focal adhesion proteins 
      Lyn/phospho-paxillin with CCR2 was also observed by co-precipitation. Inhibitor 
      studies with genistein on MCP-1-induced macrophage TNF and IL-1 production 
      additionally supported the role of protein tyrosine phosphorylation in the 
      process of macrophage activation with MCP-1. Present investigations suggest that 
      the early events in the tyrosine kinase signal transduction pathway for 
      macrophage activation in response to MCP-1 probably involve (1) CCR2 receptor 
      dimerization, (2) enhanced tyrosine phosphorylation and assembly of focal 
      adhesion complex, and (3) the activation of JAK/STAT pathway in the murine 
      peritoneal macrophages.
FAU - Biswas, Subhra Kumar
AU  - Biswas SK
AD  - School of Biotechnology, Banaras Hindu University, Varanasi, India.
FAU - Sodhi, Ajit
AU  - Sodhi A
LA  - eng
PT  - Journal Article
PL  - Netherlands
TA  - Int Immunopharmacol
JT  - International immunopharmacology
JID - 100965259
RN  - 0 (Ccr2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Milk Proteins)
RN  - 0 (Receptors, CCR2)
RN  - 0 (Receptors, Chemokine)
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (STAT5 Transcription Factor)
RN  - 0 (Stat3 protein, mouse)
RN  - 0 (Trans-Activators)
RN  - 42HK56048U (Tyrosine)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.2 (Focal Adhesion Kinase 1)
RN  - EC 2.7.10.2 (Focal Adhesion Protein-Tyrosine Kinases)
RN  - EC 2.7.10.2 (Jak1 protein, mouse)
RN  - EC 2.7.10.2 (Janus Kinase 1)
RN  - EC 2.7.10.2 (Ptk2 protein, mouse)
SB  - IM
MH  - Animals
MH  - Chemokine CCL2/*pharmacology
MH  - DNA-Binding Proteins/*physiology
MH  - Dimerization
MH  - Enzyme Inhibitors/pharmacology
MH  - Female
MH  - Focal Adhesion Kinase 1
MH  - Focal Adhesion Protein-Tyrosine Kinases
MH  - Janus Kinase 1
MH  - Macrophage Activation/drug effects/*physiology
MH  - Male
MH  - Mice
MH  - *Milk Proteins
MH  - Phosphorylation/drug effects
MH  - Protein-Tyrosine Kinases/antagonists & inhibitors/metabolism/*physiology
MH  - Receptors, CCR2
MH  - Receptors, Chemokine/biosynthesis
MH  - STAT3 Transcription Factor
MH  - STAT5 Transcription Factor
MH  - Signal Transduction/drug effects/*physiology
MH  - Trans-Activators/*physiology
MH  - Tyrosine/*metabolism/physiology
EDAT- 2002/09/28 04:00
MHDA- 2003/03/19 04:00
CRDT- 2002/09/28 04:00
PHST- 2002/09/28 04:00 [pubmed]
PHST- 2003/03/19 04:00 [medline]
PHST- 2002/09/28 04:00 [entrez]
AID - S1567-5769(02)00055-3 [pii]
AID - 10.1016/s1567-5769(02)00055-3 [doi]
PST - ppublish
SO  - Int Immunopharmacol. 2002 Jul;2(8):1095-107. doi: 10.1016/s1567-5769(02)00055-3.