PMID- 9670957
OWN - NLM
STAT- MEDLINE
DCOM- 19980730
LR  - 20131121
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 161
IP  - 2
DP  - 1998 Jul 15
TI  - The chemokine monocyte chemotactic protein 1 triggers Janus kinase 2 activation 
      and tyrosine phosphorylation of the CCR2B receptor.
PG  - 805-13
AB  - The chemokines are a growing family of low m.w., 70- to 80-residue 
      proinflammatory cytokines that operate by interacting with G protein-coupled 
      receptors. Chemokines are involved in cell migration and in the activation of 
      specific leukocyte subsets. Using the Mono Mac 1 monocytic cell line, we show 
      that monocyte chemotactic protein 1 (MCP-1) triggers activation of the Janus 
      kinase 2 (JAK2)/STAT3 pathway and CCR2 receptor tyrosine phosphorylation. Both 
      Ca2+ mobilization and cell migration are blocked in Mono Mac 1 cells by 
      tyrphostin B42, a specific JAK2 kinase inhibitor. Within seconds of MCP-1 
      activation, JAK2 phosphorylates CCR2 at the Tyr139 position and promotes 
      JAK2/STAT3 complex association to the receptor. This MCP-1-initiated 
      phosphorylation and association to JAK2 is also observed in CCR2B-transfected 
      HEK293 cells. In contrast, when a CCR2B Tyr139Phe mutant is expressed in HEK293 
      cells, it is not phosphorylated in tyrosine and triggers neither JAK2/STAT3 
      activation nor Ca2+ mobilization in response to MCP-1. These results implicate 
      the tyrosine kinase pathway in early chemokine signaling, suggesting a key role 
      for this kinase in later events.
FAU - Mellado, M
AU  - Mellado M
AD  - Department of Immunology and Oncology, Centro Nacional de Biotecnologia, Consejo 
      Superior de Investigaciones Cientifica-Universidad Autonoma de Madrid, Spain.
FAU - Rodriguez-Frade, J M
AU  - Rodriguez-Frade JM
FAU - Aragay, A
AU  - Aragay A
FAU - del Real, G
AU  - del Real G
FAU - Martin, A M
AU  - Martin AM
FAU - Vila-Coro, A J
AU  - Vila-Coro AJ
FAU - Serrano, A
AU  - Serrano A
FAU - Mayor, F Jr
AU  - Mayor F Jr
FAU - Martinez-A, C
AU  - Martinez-A C
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (CCR2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Receptors, CCR2)
RN  - 0 (Receptors, Chemokine)
RN  - 0 (Receptors, Cytokine)
RN  - 0 (Virulence Factors, Bordetella)
RN  - 42HK56048U (Tyrosine)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.2 (JAK2 protein, human)
RN  - EC 2.7.10.2 (Janus Kinase 2)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Amino Acid Substitution/genetics
MH  - Calcium/metabolism
MH  - Cell Line
MH  - Chemokine CCL2/*pharmacology
MH  - Enzyme Activation/drug effects
MH  - Humans
MH  - Janus Kinase 2
MH  - Phosphorylation
MH  - Protein-Tyrosine Kinases/drug effects/*metabolism
MH  - *Proto-Oncogene Proteins
MH  - Receptors, CCR2
MH  - Receptors, Chemokine/drug effects/*metabolism/physiology
MH  - Receptors, Cytokine/drug effects/*metabolism/physiology
MH  - Signal Transduction/drug effects
MH  - Tyrosine/genetics/*metabolism
MH  - Virulence Factors, Bordetella/pharmacology
EDAT- 1998/07/22 02:12
MHDA- 2001/03/28 10:01
CRDT- 1998/07/22 02:12
PHST- 1998/07/22 02:12 [pubmed]
PHST- 2001/03/28 10:01 [medline]
PHST- 1998/07/22 02:12 [entrez]
PST - ppublish
SO  - J Immunol. 1998 Jul 15;161(2):805-13.