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The role of beta-arrestins in the formyl peptide receptor-like 1 internalization and signaling
- Source :
- Cellular Signalling, Cellular Signalling, Elsevier, 2007, 19 (9), pp.1939-48. ⟨10.1016/j.cellsig.2007.05.006⟩, Cellular Signalling, 2007, 19 (9), pp.1939-48. ⟨10.1016/j.cellsig.2007.05.006⟩
- Publication Year :
- 2007
-
Abstract
- The N-formyl peptide receptor-like 1 (FPRL1) is a G protein-coupled receptor (GPCR) that transmits intracellular signals in response to a variety of agonists, many of them being clearly implicated in human pathology. beta-arrestins are adaptor proteins that uncouple GPCRs from G protein and regulate receptor internalization. They can also function as signal transducers through the scaffolding of signaling molecules, such as components of the extracellular signal-regulated kinase (ERK) cascade. We investigated the role of beta-arrestins in ligand-induced FPRL1 internalization and signaling. In HEK293 cells expressing FPRL1, fluorescence microscopy revealed that agonist-stimulated FPRL1 remained co-localized with beta-arrestins during endocytosis. Internalization of FPRL1, expressed in a mouse embryonic fibroblast (MEF) cell line lacking endogenous beta-arrestins, was highly compromised. This distinguishes FPRL1 from the prototypical formyl peptide receptor FPR that is efficiently internalized in the absence of beta-arrestins. In both HEK293 and MEF cells, FPRL1-mediated ERK1/2 activation was a rapid and transient event. The kinetics and extent of ERK1/2 activation were not significantly modified by beta-arrestin overexpression. The pattern of FPRL1-mediated ERK1/2 activation was similar whether cells express or not beta-arrestins. Furthermore, treatment of the FPRL1 expressing cells with pertussis toxin inhibited ERK1/2 activation in MEF and in HEK293 cells. These results led us to conclude that activation of ERK1/2 mediated by FPRL1 occurs primarily through G protein signaling. Since beta-arrestin-mediated signaling has been observed essentially for receptors coupled to G proteins other than G(i), this may be a characteristic of G(i) protein-coupled chemoattractant receptors.
- Subjects :
- MESH: Signal Transduction
Arrestins
Gene Expression
MESH: Receptors, Formyl Peptide
Mice
0302 clinical medicine
MESH: Animals
Internalization
beta-Arrestins
media_common
Mitogen-Activated Protein Kinase 1
0303 health sciences
Mitogen-Activated Protein Kinase 3
MESH: Kinetics
Signal transducing adaptor protein
Endocytosis
Cell biology
Protein Transport
MESH: Endocytosis
MESH: Arrestins
Signal transduction
MESH: Mitogen-Activated Protein Kinase 3
MESH: Mitogen-Activated Protein Kinase 1
Signal Transduction
Cell signaling
MESH: Protein Transport
MESH: Enzyme Activation
MESH: GTP-Binding Proteins
MESH: Gene Expression
G protein
media_common.quotation_subject
Recombinant Fusion Proteins
Green Fluorescent Proteins
Biology
Cell Line
03 medical and health sciences
MESH: Green Fluorescent Proteins
GTP-Binding Proteins
MESH: Recombinant Fusion Proteins
Animals
Humans
[SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology
MESH: Mice
030304 developmental biology
G protein-coupled receptor
Formyl peptide receptor
MESH: Humans
Beta-Arrestins
Cell Biology
Fibroblasts
Receptors, Formyl Peptide
MESH: Cell Line
Enzyme Activation
Kinetics
MESH: Fibroblasts
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 08986568
- Volume :
- 19
- Issue :
- 9
- Database :
- OpenAIRE
- Journal :
- Cellular signalling
- Accession number :
- edsair.doi.dedup.....f00bfd24f7cf876b40b08e2f96561adb