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Cutting edge: CXCR4-Lo: molecular cloning and functional expression of a novel human CXCR4 splice variant.




 

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



 




Information in this article was accurate in November 30, 1999. The state of the art may have changed since the publication date. This material is designed to support, not replace, the relationship that exists between you and your doctor. Always discuss treatment options with a doctor who specializes in treating HIV.