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DARC, also known as the Duffy antigen/chemokine receptor, is a seven-transmembrane protein homologous to the classical chemokine G-protein coupled receptors (GPCRs) with the exception of the motif required for G protein coupling. DARC can bind with high affinity several chemokines without transducing any signal, suggesting it may modulate the signals normally induced by these chemokines. Recently, DARC was found to interact with KAI1, a four transmembrane protein recently identified as a tumor metastasis suppressor protein. It is thought that tumor cells dislodged from the primary tumor and expressing KAI1 interact with DARC proteins expressed on vascular cells, transmitting a senescent signal to the tumor cells, while tumor cells that have lost KAI1 expression can proliferate and potentially give rise to metastases. At least three isoforms of DARC are known to exist.
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