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CUTTING EDGE |
Department of Cardiovascular Pharmacology, SmithKline Beecham Pharmaceuticals, King of Prussia, PA 19406
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 
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.
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