TY - JOUR
T1 - Cloning and functional characterization of a Na+-independent, broad-specific neutral amino acid transporter from mammalian intestine
AU - Rajan, D. Prasanna
AU - Kekuda, Ramesh
AU - Huang, Wei
AU - Devoe, Lawrence D
AU - Leibach, Frederick H.
AU - Prasad, Puttur D
AU - Ganapathy, Vadivel
N1 - Funding Information:
This work was supported by National Institutes of Health Grant HD 33347. The authors thank Vickie Mitchell for excellent secretarial assistance.
PY - 2000/1/15
Y1 - 2000/1/15
N2 - We have isolated a cDNA from a rabbit intestinal cDNA library which, when co-expressed with the heavy chain of the human 4F2 antigen (4F2hc) in mammalian cells, induces system L-like amino acid transport activity. This protein, called LAT2, consists of 535 amino acids and is distinct from LAT1 which also interacts with 4F2hc to induce system L-like amino acid transport activity. LAT2 does not interact with rBAT, a protein with a significant structural similarity to 4F2hc. The 4F2hc/LAT2-mediated transport process differs from the 4F2hc/LAT1-mediated transport in substrate specificity, substrate affinity, tissue distribution, interaction with D-amino acids, and pH-dependence. The 4F2hc/LAT2-associated transport process has a broad specificity towards neutral amino acids with K(t) values in the range of 100-1000 μM, does not interact with D-amino acids to any significant extent, and is stimulated by acidic pH. In contrast, the 4F2hc/LAT1-associated transport process has a narrower specificity towards neutral amino acids, but with comparatively higher affinity (K(t) values in the range of 10-20 μM), interacts with some D-amino acids with high affinity, and is not influenced by pH. LAT2 is expressed primarily in the small intestine and kidney, whereas LAT1 exhibits a much broader tissue distribution. Copyright (C) 2000 Elsevier Science B.V.
AB - We have isolated a cDNA from a rabbit intestinal cDNA library which, when co-expressed with the heavy chain of the human 4F2 antigen (4F2hc) in mammalian cells, induces system L-like amino acid transport activity. This protein, called LAT2, consists of 535 amino acids and is distinct from LAT1 which also interacts with 4F2hc to induce system L-like amino acid transport activity. LAT2 does not interact with rBAT, a protein with a significant structural similarity to 4F2hc. The 4F2hc/LAT2-mediated transport process differs from the 4F2hc/LAT1-mediated transport in substrate specificity, substrate affinity, tissue distribution, interaction with D-amino acids, and pH-dependence. The 4F2hc/LAT2-associated transport process has a broad specificity towards neutral amino acids with K(t) values in the range of 100-1000 μM, does not interact with D-amino acids to any significant extent, and is stimulated by acidic pH. In contrast, the 4F2hc/LAT1-associated transport process has a narrower specificity towards neutral amino acids, but with comparatively higher affinity (K(t) values in the range of 10-20 μM), interacts with some D-amino acids with high affinity, and is not influenced by pH. LAT2 is expressed primarily in the small intestine and kidney, whereas LAT1 exhibits a much broader tissue distribution. Copyright (C) 2000 Elsevier Science B.V.
KW - 4F2 heavy chain
KW - Amino acid transport
KW - Functional expression
KW - LAT2
KW - Primary structure
KW - Rabbit
KW - System L
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U2 - 10.1016/S0005-2736(99)00224-2
DO - 10.1016/S0005-2736(99)00224-2
M3 - Article
C2 - 10631289
AN - SCOPUS:0033957858
SN - 0005-2736
VL - 1463
SP - 6
EP - 14
JO - Biochimica et Biophysica Acta - Biomembranes
JF - Biochimica et Biophysica Acta - Biomembranes
IS - 1
ER -