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Details

Autor(en) / Beteiligte
Titel
The Chemokine SDF-1/CXCL12 Binds to and Signals through the Orphan Receptor RDC1 in T Lymphocytes
Ist Teil von
  • The Journal of biological chemistry, 2005-10, Vol.280 (42), p.35760-35766
Ort / Verlag
United States: Elsevier Inc
Erscheinungsjahr
2005
Quelle
MEDLINE
Beschreibungen/Notizen
  • Combined phylogenetic and chromosomal location studies suggest that the orphan receptor RDC1 is related to CXC chemokine receptors. RDC1 provides a co-receptor function for a restricted number of human immunodeficiency virus (HIV) isolates, in particular for the CXCR4-using HIV-2 ROD strain. Here we show that CXCL12, the only known natural ligand for CXCR4, binds to and signals through RDC1. We demonstrate that RDC1 is expressed in T lymphocytes and that CXCL12-promoted chemotaxis is inhibited by an anti-RDC1 monoclonal antibody. Concomitant blockade of RDC1 and CXCR4 produced additive inhibitory effects in CXCL12-induced T cell migration. Furthermore, we provide evidence that interaction of CXCL12 with RDC1 is specific, saturable, and of high affinity (apparent KD ≈ 0.4 nm). In CXCR4-negative cells expressing RDC1, CXCL12 promotes internalization of the receptor and chemotactic signals through RDC1. Collectively, our data indicate that RDC1, which we propose to rename as CXCR7, is a receptor for CXCL12.

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