The binding of stromal derived factor 1 (SDF-1) to its receptor, CXCR4, is required for the population of bone marrow by fetal hematopoietic progenitors cells, lymphopoiesisi angiogenesis and cardiac formation, and development of the cerebellum. CXCR4 plays ;k critical role in AIDS pathogenesis as a coreceptor for HIV-1 infection that is utilized by TJtropic (X4) strains of the envelope glycoprotein. To gain insight into the mechanismi involved in CXCR4 signaling, this receptor was expressed in Saccharomyces cells containing a chimeric G alpha protein. Transformation with a plasmid directing the expression o:F CXCR4 downstream of a yeast alpha factor signal peptide conferred the ability of Saccharomyces cells to grow in the presence of SDF-1 in a dose dependent fashion in the absence of histidine. Small molecule inhibitors of CXCR4, including AMDS 100, T22, anc| T140, blocked the growth stimulated by SDF-1 at concentrations in the nanomolar range! supporting the role of CXCR4 signaling in this process. Purified X4 gp!20 from the HIE and MN strains in complex with soluble CD4 appeared to induce low level growth ol[ Saccharomyces cells transformed with CXCR4 and to enhance the effect of SDP-1. This! should be a powerful approach to studying signal transduction via CXCR4 and thel interaction of this receptor with physiologic (ie SDF-1) and pathologic (ie X4 gpl20J ligands.
|Original language||English (US)|
|Issue number||11 PART I|
|State||Published - 2000|
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