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

• DOI: 10.1073/pnas.93.25.14726
• Publication Date: 2002-07-26T14:43:20Z
• Authors: Takashi Nagasawa; Toshihiro Nakajima; Kazunobu Tachibana; Hisashi Iizasa; Conrad C. Bleul; Osamu Yoshie; Kouji Matsushima; Nobuaki Yoshida; Timothy A. Springer; Tadamitsu Kishimoto
• Keywords: Adult; 0301 basic medicine; Receptors, CXCR4; Molecular Sequence Data; Membrane Proteins; Chemokine CXCL12; 3. Good health; Mice; 03 medical and health sciences; Receptors, HIV; Cricetinae; Animals; Cytokines; Humans; Amino Acid Sequence; Cloning, Molecular; Receptors, Cytokine; Chemokines, CXC; Sequence Analysis; Signal Transduction

Pre-B-cell growth-stimulating factor/stromal cell-derived factor 1 (PBSF/SDF-1) is a member of the CXC 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 perinatal viability, B lymphopoiesis, bone marrow myelopoiesis, and cardiac ventricular septal formation, and it has chemotactic activities on resting lymphocytes and monocytes. In this paper, we have isolated a cDNA that encodes a seven transmembrane-spanning-domain receptor, designated pre-B-cell-derived chemokine receptor (PB-CKR) from a murine pre-B-cell clone, DW34. The deduced amino acid sequence has 90% identity with that of a HUMSTSR/fusin, a human immunodeficiency virus 1 (HIV-1) entry coreceptor. However, the second extracellular region has lower identity (67%) compared with HUMSTSR/fusin. PB-CKR is expressed during embryo genesis and in many organs and T cells of adult mice. Murine PBSF/SDF-1 induced an increase in intracellular free Ca 2+ in DW34 cells and PB-CKR-transfected Chinese hamster ovary (CHO) cells, suggesting that PB-CKR is a functional receptor for murine PBSF/SDF-1. Murine PBSF/SDF-1 also induced Ca 2+ influx in fusin-transfected CHO cells. On the other hand, considering previous results that HIV-1 does not enter murine T cells that expressed human CD4, PB-CKR may not support HIV-1 infection. Thus, PB-CKR will be an important tool for functional mapping of HIV-1 entry coreceptor fusin and for understanding the function of PBSF/SDF-1 further.