Molecular cloning and functional expression of two monocyte chemoattractant protein 1 receptors reveals alternative splicing of the carboxyl-terminal tails.

Charo, Israel F.; Myers, Scott J.; Herman, Ann; Franci, Christian; Connolly, Andrew J.; Coughlin, Shaun R.

doi:10.1073/pnas.91.7.2752

Cited by 653 publications

(526 citation statements)

References 35 publications

Supporting

Mentioning

510

Contrasting

Unclassified

Order By: Relevance

“…Splice variants of chemokine receptors are not common, but they are also not unprecedented. C-terminal splice variants are found for CXCR1 (24), CXCR2 (24), and CCR2 (25). Alternative splicing of the N-terminus of chemokine receptors has previously been described for CXCR3 and CXCR4 (26).…”

Section: Discussionmentioning

confidence: 92%

“…The receptor still binds stromal cell-derived factor 1, but exhibits reduced calcium flux and migration (27) compared with the wild-type receptor. Since the N-terminal region is important for receptor activation of CCR2 (25), it is hypothesized that the alternative splice variant may alter the functional responsiveness of this receptor to its ligand.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Up‐regulated expression and activation of the orphan chemokine receptor, CCRL2, in rheumatoid arthritis

Galligan¹,

Matsuyama²,

Matsukawa³

et al. 2004

Arthritis & Rheumatism

View full text Add to dashboard Cite

Objective. Rheumatoid arthritis (RA) is a chronic inflammatory condition characterized by a cellular influx and destruction of the joint architecture. Chemokines characteristically regulate leukocyte recruitment and activation. Chemokine (CC motif) receptor-like 2 (CCRL2) is an orphan receptor with homology to other CC chemokine receptors. We undertook this study to examine CCRL2 expression in RA, cytokine regulation of expression, and the source of a putative ligand in an attempt to determine the role of this receptor during inflammation.Methods. Expression of CCRL2 on joint-infiltrating leukocytes was examined by immunocytochemistry. In vitro studies evaluated CCRL2 expression in primary neutrophils using Northern and Western blotting and reverse transcriptase-polymerase chain reaction. HEK 293 cells expressing two splice variants of CCRL2 (HEK/CCRL2A or HEK/CCRL2B) were generated with a retroviral expression system, and their migration in response to fractions of synovial fluid (SF) from RA patients was examined using a 48-well chamber.Results. CCRL2 expression was observed on all infiltrating neutrophils and on some macrophages obtained from the SF of 5 RA patients. In vitro studies of primary neutrophils revealed that CCRL2 messenger RNA (mRNA) was rapidly up-regulated following stimulation with lipopolysaccharide (1 g/ml) or tumor necrosis factor (5 ng/ml). The mRNA for both CCRL2A and CCRL2B were expressed in cytokinestimulated neutrophils. Cells expressing either of these splice variants migrated in response to a fraction of RA SF.Conclusion. CCRL2 expression is up-regulated on synovial neutrophils of RA patients. Inflammatory products present in the SF activate this receptor, indicating that CCRL2 is a functional receptor that may be involved in the pathogenesis of RA.

show abstract

Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Up‐regulated expression and activation of the orphan chemokine receptor, CCRL2, in rheumatoid arthritis

Galligan¹,

Matsuyama²,

Matsukawa³

et al. 2004

Arthritis & Rheumatism

View full text Add to dashboard Cite

show abstract

“…3), specific receptors for MCP-1 and s-FKN, respectively described (22,33), and 2) incubation of MonoMac6 cells with s-FKN did not modify the level of membrane-associated CCR2 (Fig. 4), ruling out the possibility that s-FKN impairs MonoMac6 migration through the down-regulation of the MCP-1R.…”

Section: S-fkn Directly Exerts Its Inhibitory Effect On Monomac 6 Celmentioning

confidence: 99%

Soluble Fractalkine Prevents Monocyte Chemoattractant Protein-1-Induced Monocyte Migration via Inhibition of Stress-Activated Protein Kinase 2/p38 and Matrix Metalloproteinase Activities

Vitale

Schmid-Alliana

Breuil

et al. 2004

The Journal of Immunology

View full text Add to dashboard Cite

In this study, we address the question of the cross-talk between two chemokines that are cosecreted during inflammation, namely monocyte chemoattractant protein-1 (MCP-1) and soluble fractalkine (s-FKN), toward monocyte migration. We found that s-FKN fails to induce MonoMac6 cell migration per se. Interestingly, this chemokine antagonizes transendothelial migration and chemotaxis of MonoMac6 cells and freshly isolated human monocytes induced by MCP-1, indicating a direct effect of s-FKN on monocytic cells. In this study, we found that stress-activated protein kinase (SAPK)1/c-Jun N-terminal kinase 1 and SAPK2/p38 are involved in the control of MCP-1-induced MonoMac6 cell migration. We demonstrated that s-FKN abrogates the MCP-1-induced SAPK2/p38 activation as well as the upstream Pyk2 activity. Furthermore, we observed that s-FKN also inhibits the activity of a major matrix metalloproteinase (MMP), namely MMP-2. Taken collectively, our results indicate that the s-FKN antagonizes the chemoattractant effect of MCP-1 on monocytes, likely by inhibiting crucial signaling pathways, like SAPK2/p38 and MMP-2 activities.

show abstract

“…The first CC chemokine receptor cloned, CC CKR-1 [6,7] was shown to be a shared receptor for two members of this sub-class, RAN-TES and MIP-I~. Subsequently, a second CC chemokine receptor, CC CKR-2, was identified as being a high affinity receptor for MCP-1 [8]. Recently two new RANTES/MIP<z receptors have been cloned: CC CKR-3 which is expressed in eosinophils [9] and CC CKR-4 from a basophilic cell line, KU812 [10].…”

Section: Introductionmentioning

confidence: 99%

Characterisation of the RANTES/MIP‐1α receptor (CC CKR‐1) stably transfected in HEK 293 cells and the recombinant ligands

Proudfoot¹,

Power²,

Hoogewerf³

et al. 1995

FEBS Letters

View full text Add to dashboard Cite

The CC chemokines RANTES and MIP-I~ are known to activate certain leucocytes and leucocytie cell lines. We have produced and fully cbaracterised the recombinant proteins expressed in E. coil They induce ehemotaxis of the pro-monoc)tic cell line, THP-1 and T cells. THP-1 cells express three of the known CC chemokine receptors. In order to study the activation of a single receptor, we have expressed the shared receptor ((C CKR-1) for RANTES and MIP-la stably in the HEK 293 cell line. We have examined the effects of RANTES and MIP-la on the CC CKR-1 transfectants by equilibrium binding studies and in a ebemotaxis assay. RANTES competes for pZSlIRAN-TES with an ICs0 of 0.6 + 0.23 nM, whereas MIP-la competes for its radiolabelled counterpart with an ICs0 of 10 + 1.6 nM in the transfeetants. These affinities are the same as those measured on the THP-1 call line. The stably transfected HEK 293 cells respond to both these chemokines in the chemotaxis assay with the same ECso values as those measured for THP-1 cells. This indicates that this cellular response can be mediated through the CC CKR-1 receptor.

show abstract

Molecular cloning and functional expression of two monocyte chemoattractant protein 1 receptors reveals alternative splicing of the carboxyl-terminal tails.

Abstract: Monocyte chemoattractant protein 1 (MCP-1) is a member of the chemokine family of cytokines that mediate leukocyte chemotaxis.

Cited by 653 publications

References 35 publications

Up‐regulated expression and activation of the orphan chemokine receptor, CCRL2, in rheumatoid arthritis

Up‐regulated expression and activation of the orphan chemokine receptor, CCRL2, in rheumatoid arthritis

Soluble Fractalkine Prevents Monocyte Chemoattractant Protein-1-Induced Monocyte Migration via Inhibition of Stress-Activated Protein Kinase 2/p38 and Matrix Metalloproteinase Activities

Characterisation of the RANTES/MIP‐1α receptor (CC CKR‐1) stably transfected in HEK 293 cells and the recombinant ligands

Contact Info

Product

Resources

About