Back to Search
Start Over
Phosphoproteomic characterization of the signaling network resulting from activation of the chemokine receptor CCR2
- Source :
- J Biol Chem
- Publication Year :
- 2020
- Publisher :
- Elsevier BV, 2020.
-
Abstract
- Leukocyte recruitment is a universal feature of tissue inflammation and regulated by the interactions of chemokines with their G protein–coupled receptors. Activation of CC chemokine receptor 2 (CCR2) by its cognate chemokine ligands, including CC chemokine ligand 2 (CCL2), plays a central role in recruitment of monocytes in several inflammatory diseases. In this study, we used phosphoproteomics to conduct an unbiased characterization of the signaling network resulting from CCL2 activation of CCR2. Using data-independent acquisition MS analysis, we quantified both the proteome and phosphoproteome in FlpIn-HEK293T cells stably expressing CCR2 at six time points after activation with CCL2. Differential expression analysis identified 699 significantly regulated phosphorylation sites on 441 proteins. As expected, many of these proteins are known to participate in canonical signal transduction pathways and in the regulation of actin cytoskeleton dynamics, including numerous guanine nucleotide exchange factors and GTPase-activating proteins. Moreover, we identified regulated phosphorylation sites in numerous proteins that function in the nucleus, including several constituents of the nuclear pore complex. The results of this study provide an unprecedented level of detail of CCR2 signaling and identify potential targets for regulation of CCR2 function.
- Subjects :
- Proteomics
0301 basic medicine
CCR2
Chemokine
Cell signaling
Receptors, CCR2
Biochemistry
03 medical and health sciences
Chemokine receptor
Humans
Phosphorylation
Molecular Biology
030102 biochemistry & molecular biology
biology
Chemistry
Phosphoproteomics
Cell Biology
Phosphoproteins
Actin cytoskeleton
Cell biology
Gene Ontology
HEK293 Cells
030104 developmental biology
biology.protein
Signal transduction
CC chemokine receptors
Signal Transduction
Subjects
Details
- ISSN :
- 00219258
- Volume :
- 295
- Database :
- OpenAIRE
- Journal :
- Journal of Biological Chemistry
- Accession number :
- edsair.doi.dedup.....505094ce6d8180f3c2d2c90451084238