Cell-surface receptor for ecotropic murine retroviruses is a basic amino-acid transporter

Wang, Hao; Kavanaugh, Michael P.; North, R A; Kabat, David

doi:10.1038/352729a0

Cited by 422 publications

(265 citation statements)

References 26 publications

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“…This cDNA is predicted to encode a hydrophobic protein with 14 membrane-span ning regions, creating seven extracellular and eight in tracellular domains. Sequence analysis suggested homol ogy to yeast amino acid permeases (Cooper 1982;Hoff mann 1985;Tanaka and Fink 1985;Weber et al 1988), an observation corroborated when injection of mCAT-1 mRNA into Xenopus oocytes resulted in increased up take of the cationic amino acids arginine, lysine, and ornithine (Kim et al 1991;Wang et al 1991). These amino acids are considered either essential or indispens able in rodents because they are synthesized at low lev els or not at all (for review, see Visek 1986).…”

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confidence: 73%

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Anemia and perinatal death result from loss of the murine ecotropic retrovirus receptor mCAT-1.

Perkins

Mar²,

Shutter³

et al. 1997

Genes Dev.

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The mCAT-1 gene encodes a basic amino acid transporter that also acts as the receptor for murine ecotropic leukemia viruses. Targeted mutagenesis in embryonic stem cells has been used to introduce a germ-line null mutation into this gene. This mutation removes a domain critical for virus binding and inactivates amino acid transport activity. Homozygous mutant pups generated from these cells were -25% smaller than normal littermates, very anemic, and died on the day of birth. Peripheral blood from homozygotes contained 50% fewer red blood cells, reduced hemoglobin levels, and showed a pronounced normoblastosis. Histological analyses of bone marrow, spleen, and liver showed a decrease in both erythroid progenitors and mature red blood cells. Mutant fetal liver cells behaved normally in in vitro hematopoietic colony-forming assays but generated an anemia when transplanted into irradiated C.B.-17 SCID mice. Furthermore, reconstitution of the white cell compartment of SCID mice by mutant fetal liver cells was less complete than that observed with a mixed population of wild-type and heterozygous fetal liver cells. Primary embryo fibroblasts from mutant mice were completely resistant to ecotropic retrovirus infection. Thus, mCAT-1 not only appears to be the sole receptor for a group of murine ecotropic retroviruses associated with hematological disease but also plays a critical role in both hematopoiesis and growth control during mouse development.

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confidence: 73%

“…The murine cationic amino acid transporter 1 (mCAT-1) protein mediates type C ecotropic retrovirus infection of mouse cells by acting as a receptor for viral envelope proteins (Albritton et al 1989;Wang et al 1991). The mCAT-1 cDNA was cloned by virtue of its ability to make otherwise resistant human cells sensitive to infec tion (Albritton et al 1989).…”

mentioning

confidence: 99%

Anemia and perinatal death result from loss of the murine ecotropic retrovirus receptor mCAT-1.

Perkins

Mar²,

Shutter³

et al. 1997

Genes Dev.

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“…However, we believe it is more likely that induction of arginine transport by LPS is regulated independently of the intracellular metabolism of arginine. Investigation of the regulatory sequence of the system y+ gene, recently identified (Kim et al, 1991;Wang et al, 1991), will be needed to substantiate this hypothesis.…”

Section: Discussionmentioning

confidence: 99%

Selective inhibition by dexamethasone of induction of NO synthase, but not of induction of l‐arginine transport, in activated murine macrophage J774 cells

Baydoun

Bogle

Pearson

et al. 1993

British J Pharmacology

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1 Effects of dexamethasone on induction of nitric oxide (NO) synathase and L-arginine transport by lipopolysaccharide (LPS) were examined in a murine cultured macrophage cell line J774. Metabolism of L-arginine to L-citrulline and subsequent changes in intracellular amino acids pools were correlated with changes in nitrite production. 3 Induction of NO synthase by LPS (1 jig ml-', 24 h) alone was accompanied by a marked increase in arginine utilisation leading to decreased intracellular arginine levels and elevated intracellular and extracellular L-citrulline levels. These changes were further enhanced in the presence of interferon-y (IFN-y, 100 units ml-', 24h).4 Dexamethasone (1 jaM) abolished the increases in both nitrite and citrulline production induced by LPS alone but only partially reversed the combined effects of LPS and IFN-y. In contrast, treatment of cells with dexamethasone (10 jtM) had no effect on the LPS-mediated induction of arginine transport or the decrease in intracellular arginine concentration. 5 We conclude that induction of arginine transporter activity in LPS-stimulated J774 cells involves de novo synthesis of carrier proteins, which increases transport of exogenous arginine during enhanced NO production. Moreover, the intracellular signalling pathways mediating induction of arginine transport and of NO synthase by LPS in activated macrophages diverge, since only the latter is sensitive to dexamethasone.

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“…Normal human urothelial cells were transduced with an amphotropic retrovirus encoding the ecotropic retrovirus receptor (Wang et al, 1991) and then transduced with ecotropic retroviruses encoding p53DD, Id-1, CDK4 R24C or hTERT. Vectors used were pWZL Eco receptor neo, pBabe hTERT puro, pBabe p53DD puro.…”

Section: Retroviral Transductionmentioning

confidence: 99%

Expression of hTERT immortalises normal human urothelial cells without inactivation of the p16/Rb pathway

et al. 2006

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The CDKN2A locus is frequently inactivated in urothelial cell carcinoma (UCC), yet how this alteration contributes to bladder tumorigenesis is not known. Although most UCC express telomerase, inactivation of the p16/Rb pathway is generally required for in vitro immortalisation. This and the involvement of p16 in senescence of normal human urothelial cells (NHUC) suggest that CDKN2A deletion may aid bypass of senescence and allow immortalisation. CDKN2A encodes p16 and p14 ARF and therefore inactivation of this locus can disrupt both the Rb and p53 tumour suppressor pathways. Retrovirusmediated transduction was used to specifically modulate the p16/Rb and/or p53 tumour suppressor pathways in NHUC and to express human telomerase reverse transcriptase (hTERT). Expression of hTERT bypassed Rb and p53 pathway-dependent barriers to proliferation and immortalised NHUC. TERT-NHUC had normal karyotypes, were non-tumorigenic and unexpectedly retained CDKN2A. Thus, the phenotypic significance of inactivation of CDKN2A in UCC may not be solely related to bypass of senescence. Phenotypic assays in human urothelial cells have relied on cell strains derived from invasive tumours or NHUC immortalised by expression of SV40-large T. The production of genetically normal but immortal NHUC lines now provides a valuable platform for experiments to examine the timing and combination of events necessary for UCC tumorigenesis.

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Cell-surface receptor for ecotropic murine retroviruses is a basic amino-acid transporter

Cited by 422 publications

References 26 publications

Anemia and perinatal death result from loss of the murine ecotropic retrovirus receptor mCAT-1.

Anemia and perinatal death result from loss of the murine ecotropic retrovirus receptor mCAT-1.

Selective inhibition by dexamethasone of induction of NO synthase, but not of induction of l‐arginine transport, in activated murine macrophage J774 cells

Expression of hTERT immortalises normal human urothelial cells without inactivation of the p16/Rb pathway

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