Expression of functional cxcr4 in saccharomyces cells

a model system for analysis of receptor interactions

Wenbo Zhang, Zixuan Wang, John F J Manfredi, Nobutaka Fujii, Gang Pei, James R. Broach, Stephen C. Peiper

Research output: Contribution to journalArticle

Abstract

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 languageEnglish (US)
JournalBlood
Volume96
Issue number11 PART I
StatePublished - 2000
Externally publishedYes

Fingerprint

Saccharomyces
Systems Analysis
CXCR4 Receptors
Signal transduction
Protein Sorting Signals
Histidine
Yeast
Glycoproteins
Bone
Plasmids
Growth
Hematopoietic Stem Cells
Ligands
Cerebellum
Molecules
HIV Infections
HIV-1
Signal Transduction
Acquired Immunodeficiency Syndrome
Yeasts

ASJC Scopus subject areas

  • Hematology

Cite this

Zhang, W., Wang, Z., Manfredi, J. F. J., Fujii, N., Pei, G., Broach, J. R., & Peiper, S. C. (2000). Expression of functional cxcr4 in saccharomyces cells: a model system for analysis of receptor interactions. Blood, 96(11 PART I).

Expression of functional cxcr4 in saccharomyces cells : a model system for analysis of receptor interactions. / Zhang, Wenbo; Wang, Zixuan; Manfredi, John F J; Fujii, Nobutaka; Pei, Gang; Broach, James R.; Peiper, Stephen C.

In: Blood, Vol. 96, No. 11 PART I, 2000.

Research output: Contribution to journalArticle

Zhang, W, Wang, Z, Manfredi, JFJ, Fujii, N, Pei, G, Broach, JR & Peiper, SC 2000, 'Expression of functional cxcr4 in saccharomyces cells: a model system for analysis of receptor interactions', Blood, vol. 96, no. 11 PART I.
Zhang W, Wang Z, Manfredi JFJ, Fujii N, Pei G, Broach JR et al. Expression of functional cxcr4 in saccharomyces cells: a model system for analysis of receptor interactions. Blood. 2000;96(11 PART I).
Zhang, Wenbo ; Wang, Zixuan ; Manfredi, John F J ; Fujii, Nobutaka ; Pei, Gang ; Broach, James R. ; Peiper, Stephen C. / Expression of functional cxcr4 in saccharomyces cells : a model system for analysis of receptor interactions. In: Blood. 2000 ; Vol. 96, No. 11 PART I.
@article{90853b4208b84dd8b57444fd88eb1982,
title = "Expression of functional cxcr4 in saccharomyces cells: a model system for analysis of receptor interactions",
abstract = "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.",
author = "Wenbo Zhang and Zixuan Wang and Manfredi, {John F J} and Nobutaka Fujii and Gang Pei and Broach, {James R.} and Peiper, {Stephen C.}",
year = "2000",
language = "English (US)",
volume = "96",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "11 PART I",

}

TY - JOUR

T1 - Expression of functional cxcr4 in saccharomyces cells

T2 - a model system for analysis of receptor interactions

AU - Zhang, Wenbo

AU - Wang, Zixuan

AU - Manfredi, John F J

AU - Fujii, Nobutaka

AU - Pei, Gang

AU - Broach, James R.

AU - Peiper, Stephen C.

PY - 2000

Y1 - 2000

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=33748659515&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33748659515&partnerID=8YFLogxK

M3 - Article

VL - 96

JO - Blood

JF - Blood

SN - 0006-4971

IS - 11 PART I

ER -