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Cutting edge: CXCR4-Lo: molecular cloning and functional expression of a novel human CXCR4 splice variant.
Gupta SK; Pillarisetti K; Department of Cardiovascular Pharmacology,
November 30, 1999
J Immunol. 1999 Sep 1;163(5):2368-72. Unique Identifier : AIDSLINE

Human CXCR4 is a specific receptor for the CXC chemokine stromal cell-derived factor-1 (SDF-1) and a coreceptor for T cell line tropic strains of HIV-1. Genetic knockouts of CXCR4 and SDF-1 have delineated their critical role during embryonic cardiogenesis, leukopoiesis, and vasculogenesis. Herein, we used bioinformatics and differential strategies like isoform-specific RT-PCR and Northern blots to identify and clone a novel unspliced isoform of human CXCR4, termed CXCR4-Lo. CXCR4-Lo corresponds to a larger approximately 4. 0-kb mRNA transcript and differs from the known human CXCR4 by the first 9 aa in the functionally important NH2-terminal extracellular domain of the receptor. CXCR4-Lo-transfected rat basophil leukemia-2H3 cells responded to SDF-1 with a transient rise of intracellular Ca2+ concentration and by undergoing chemotaxis. Expression of CXCR4-Lo is noteworthy, as it may have differential affinity as a coreceptor for HIV strains in comparison with CXCR4. Furthermore, CXCR4-Lo may also provide a functional backup to CXCR4 during embryogenesis.

JOURNAL ARTICLE Alternative Splicing/*IMMUNOLOGY Amino Acid Sequence Animal Base Sequence Chemokines, CXC/PHARMACOLOGY Chemotaxis, Leukocyte/IMMUNOLOGY Cloning, Molecular Comparative Study DNA, Complementary/CHEMISTRY/ISOLATION & PURIF Human Leukemia, Basophilic, Acute Molecular Sequence Data Rats Receptors, CXCR4/*BIOSYNTHESIS/*GENETICS/IMMUNOLOGY/ISOLATION & PURIF Transfection Tumor Cells, Cultured

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