Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
EMBO J
1999 Jan 04;181:49-57. doi: 10.1093/emboj/18.1.49.
Show Gene links
Show Anatomy links
Amino acid transport of y+L-type by heterodimers of 4F2hc/CD98 and members of the glycoprotein-associated amino acid transporter family.
Pfeiffer R
,
Rossier G
,
Spindler B
,
Meier C
,
Kühn L
,
Verrey F
.
???displayArticle.abstract???
Amino acid transport across cellular membranes is mediated by multiple transporters with overlapping specificities. We recently have identified the vertebrate proteins which mediate Na+-independent exchange of large neutral amino acids corresponding to transport system L. This transporter consists of a novel amino acid permease-related protein (LAT1 or AmAT-L-lc) which for surface expression and function requires formation of disulfide-linked heterodimers with the glycosylated heavy chain of the h4F2/CD98 surface antigen. We show that h4F2hc also associates with other mammalian light chains, e.g. y+LAT1 from mouse and human which are approximately 48% identical with LAT1 and thus belong to the same family of glycoprotein-associated amino acid transporters. The novel heterodimers form exchangers which mediate the cellular efflux of cationic amino acids and the Na+-dependent uptake of large neutral amino acids. These transport characteristics and kinetic and pharmacological fingerprints identify them as y+L-type transport systems. The mRNA encoding my+LAT1 is detectable in most adult tissues and expressed at high levels in kidney cortex and intestine. This suggests that the y+LAT1-4F2hc heterodimer, besides participating in amino acid uptake/secretion in many cell types, is the basolateral amino acid exchanger involved in transepithelial reabsorption of cationic amino acids; hence, its defect might be the cause of the human genetic disease lysinuric protein intolerance.
Albritton,
A putative murine ecotropic retrovirus receptor gene encodes a multiple membrane-spanning protein and confers susceptibility to virus infection.
1989, Pubmed
Albritton,
A putative murine ecotropic retrovirus receptor gene encodes a multiple membrane-spanning protein and confers susceptibility to virus infection.
1989,
Pubmed
Angelo,
The binding specificity of amino acid transport system y+L in human erythrocytes is altered by monovalent cations.
1996,
Pubmed
Angelo,
Amino acid transport system y+L of human erythrocytes: specificity and cation dependence of the translocation step.
1994,
Pubmed
Bertran,
Stimulation of system y(+)-like amino acid transport by the heavy chain of human 4F2 surface antigen in Xenopus laevis oocytes.
1992,
Pubmed
,
Xenbase
Bröer,
Expression of the surface antigen 4F2hc affects system-L-like neutral-amino-acid-transport activity in mammalian cells.
1997,
Pubmed
Bröer,
Discrimination of two amino acid transport activities in 4F2 heavy chain- expressing Xenopus laevis oocytes.
1998,
Pubmed
,
Xenbase
Bröer,
The 4F2hc surface antigen is necessary for expression of system L-like neutral amino acid-transport activity in C6-BU-1 rat glioma cells: evidence from expression studies in Xenopus laevis oocytes.
1995,
Pubmed
,
Xenbase
Chillarón,
Obligatory amino acid exchange via systems bo,+-like and y+L-like. A tertiary active transport mechanism for renal reabsorption of cystine and dibasic amino acids.
1996,
Pubmed
,
Xenbase
Christensen,
Gene-product designations for amino acid transporters.
1994,
Pubmed
Devés,
Transporters for cationic amino acids in animal cells: discovery, structure, and function.
1998,
Pubmed
,
Xenbase
Devés,
Identification of a new transport system (y+L) in human erythrocytes that recognizes lysine and leucine with high affinity.
1992,
Pubmed
Devés,
Changes in membrane and surface potential explain the opposite effects of low ionic strength on the two lysine transporters of human erythrocytes.
1996,
Pubmed
Devés,
N-ethylmaleimide discriminates between two lysine transport systems in human erythrocytes.
1993,
Pubmed
Dixon,
Isolation and characterization of a heterodimeric surface antigen on human melanoma cells and evidence that it is the 4F2 cell activation/proliferation molecule.
1990,
Pubmed
Fei,
The amino acid transport system y+L induced in Xenopus laevis oocytes by human choriocarcinoma cell (JAR) mRNA is functionally related to the heavy chain of the 4F2 cell surface antigen.
1995,
Pubmed
,
Xenbase
Fenczik,
Complementation of dominant suppression implicates CD98 in integrin activation.
1997,
Pubmed
Geering,
A role for the beta-subunit in the expression of functional Na+-K+-ATPase in Xenopus oocytes.
1989,
Pubmed
,
Xenbase
Haynes,
Characterization of a monoclonal antibody (4F2) that binds to human monocytes and to a subset of activated lymphocytes.
1981,
Pubmed
Hemler,
Characterization of antigen recognized by the monoclonal antibody (4F2): different molecular forms on human T and B lymphoblastoid cell lines.
1982,
Pubmed
Kanai,
Expression cloning and characterization of a transporter for large neutral amino acids activated by the heavy chain of 4F2 antigen (CD98).
1998,
Pubmed
,
Xenbase
Kim,
Transport of cationic amino acids by the mouse ecotropic retrovirus receptor.
1991,
Pubmed
,
Xenbase
Lennon,
The I.M.A.G.E. Consortium: an integrated molecular analysis of genomes and their expression.
1996,
Pubmed
Lüscher,
Biosynthesis and maturation of the Lyt-2/3 molecular complex in mouse thymocytes.
1985,
Pubmed
Mastroberardino,
Amino-acid transport by heterodimers of 4F2hc/CD98 and members of a permease family.
1998,
Pubmed
,
Xenbase
Nagase,
Prediction of the coding sequences of unidentified human genes. VI. The coding sequences of 80 new genes (KIAA0201-KIAA0280) deduced by analysis of cDNA clones from cell line KG-1 and brain.
1996,
Pubmed
Parmacek,
Structure, expression and regulation of the murine 4F2 heavy chain.
1989,
Pubmed
Pfeiffer,
Functional heterodimeric amino acid transporters lacking cysteine residues involved in disulfide bond.
1998,
Pubmed
,
Xenbase
Pickel,
Ultrastructural localization of a neutral and basic amino acid transporter in rat kidney and intestine.
1993,
Pubmed
Puoti,
Novel isoforms of the beta and gamma subunits of the Xenopus epithelial Na channel provide information about the amiloride binding site and extracellular sodium sensing.
1997,
Pubmed
,
Xenbase
Quackenbush,
Differential localization within human kidney of five membrane proteins expressed on acute lymphoblastic leukemia cells.
1986,
Pubmed
Rajantie,
Lysinuric protein intolerance. Basolateral transport defect in renal tubuli.
1981,
Pubmed
Smith,
Lysinuric protein intolerance mutation is expressed in the plasma membrane of cultured skin fibroblasts.
1987,
Pubmed
Spindler,
Characterization of early aldosterone-induced RNAs identified in A6 kidney epithelia.
1997,
Pubmed
,
Xenbase
Teixeira,
Primary structure of the human 4F2 antigen heavy chain predicts a transmembrane protein with a cytoplasmic NH2 terminus.
1987,
Pubmed
Wang,
Cell-surface receptor for ecotropic murine retroviruses is a basic amino-acid transporter.
1991,
Pubmed
,
Xenbase
Wang,
Oligomeric structure of a renal cystine transporter: implications in cystinuria.
1995,
Pubmed
,
Xenbase
Wells,
Cloning of a rat kidney cDNA that stimulates dibasic and neutral amino acid transport and has sequence similarity to glucosidases.
1992,
Pubmed
,
Xenbase
Wells,
The 4F2 antigen heavy chain induces uptake of neutral and dibasic amino acids in Xenopus oocytes.
1992,
Pubmed
,
Xenbase
Yagita,
Inhibition of tumor cell growth in vitro by murine monoclonal antibodies that recognize a proliferation-associated cell surface antigen system in rats and humans.
1986,
Pubmed
