MOLECULAR-CLONING AND CHARACTERIZATION OF A MURINE PRE-B-CELL GROWTH-STIMULATING FACTOR STROMAL CELL-DERIVED FACTOR-1 RECEPTOR, A MURINE HOMOLOG OF THE HUMAN-IMMUNODEFICIENCY-VIRUS-1 ENTRY CORECEPTOR FUSIN

Pre-B-cell growth-stimulating factor/stromal cell-derived factor 1 (PB SF/SDF-1) is a member of the CSC group of chemokines that is initially identified as a bone marrow stromal cell-derived factor and as a pre- B-cell stimulatory factor, Although most chemokines are thought to be inducible inflammatory mediators, PBSF/SDF-1 is essential for perinata l viability, B lymphopoiesis, bone marrow myelopoiesis, and cardiac ve ntricular septal formation, and it has chemotactic activities on resti ng lymphocytes and monocytes, In this paper, we hare isolated a cDNA t hat encodes a seven transmembrane-spanning-domain receptor, designated pre-B-cell-derived chemokine receptor (PB-CKR) from a murine pre-B-ce ll door, DW34. The deduced amino acid sequence has 90% identity with t hat of a HUMSTSR/fusin, a human immunodeficiency virus 1 (HIV-1) entry coreceptor, However, the second extracellular region has lower identi ty (67%) compared with HUMSTSR/fusin. PB-CKR is expressed during embry o genesis and in many organs and T cells of adult mice, Murine PBSF/SD F-1 induced an increase in intracellular free Ca2+ in DW35 cells and P B-CKR-transfected Chinese hamster ovary (CHO) cells, suggesting that P B-CKR is a functional receptor for murine PBSF/SDF-1. Murine PBSF/SDF- 1 also induced Ca2+ influx in fusin-transfected CHO cells, On the othe r hand, considering previous results that HIV-1 does not enter murine T cells that expressed human CD4, PB-CKR may not support HIV-1 infecti on, Thus, PB-CKR HIV-1 will be an important tool for functional mappin g of HIV-1 entry coreceptor fusin and for understanding the function o f PBSF/SDF-1 further.