PMID- 10391916
OWN - NLM
STAT- MEDLINE
DCOM- 19990805
LR  - 20190508
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 28
DP  - 1999 Jul 9
TI  - Identification and functional characterization of a Na+-independent neutral amino
      acid transporter with broad substrate selectivity.
PG  - 19745-51
AB  - We have isolated a cDNA from rat small intestine that encodes a novel
      Na+-independent neutral amino acid transporter with distinctive characteristics
      in substrate selectivity and transport property. The encoded protein, designated 
      L-type amino acid transporter-2 (LAT-2), shows amino acid sequence similarity to 
      the system L Na+-independent neutral amino acid transporter LAT-1 (Kanai, Y.,
      Segawa, H., Miyamoto, K., Uchino, H., Takeda, E., and Endou, H. (1998) J. Biol.
      Chem. 273, 23629-23632) (50% identity) and the system y+L transporters y+LAT-1
      (47%) and KIAA0245/y+LAT-2 (45%) (Torrents, D., Estevez, R., Pineda, M.,
      Fernandez, E., Lloberas, J., Shi, Y.-B., Zorzano, A., and Palacin, M. (1998) J.
      Biol. Chem. 273, 32437-32445). LAT-2 is a nonglycosylated membrane protein. It
      requires 4F2 heavy chain, a type II membrane glycoprotein, for its functional
      expression in Xenopus oocytes. LAT-2-mediated transport is not dependent on Na+
      or Cl- and is inhibited by a system L-specific inhibitor,
      2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH), indicating that LAT-2 is 
      a second isoform of the system L transporter. Compared with LAT-1, which prefers 
      large neutral amino acids with branched or aromatic side chains, LAT-2 exhibits
      remarkably broad substrate selectivity. It transports all of the L-isomers of
      neutral alpha-amino acids. LAT-2 exhibits higher affinity (Km = 30-50 microM) to 
      Tyr, Phe, Trp, Thr, Asn, Ile, Cys, Ser, Leu, Val, and Gln and relatively lower
      affinity (Km = 180-300 microM) to His, Ala, Met, and Gly. In addition, LAT-2
      mediates facilitated diffusion of substrate amino acids, as distinct from LAT-1, 
      which mediates amino acid exchange. LAT-2-mediated transport is increased by
      lowering the pH level, with peak activity at pH 6.25, because of the decrease in 
      the Km value without changing the Vmax value. Because of these functional
      properties and a high level of expression of LAT-2 in the small intestine,
      kidney, placenta, and brain, it is suggested that the heterodimeric complex of
      LAT-2 and 4F2 heavy chain is involved in the trans-cellular transport of neutral 
      amino acids in epithelia and blood-tissue barriers.
FAU - Segawa, H
AU  - Segawa H
AD  - Department of Pharmacology and Toxicology, Kyorin University School of Medicine, 
      6-20-2 Shinkawa, Mitaka, Tokyo 181-8611, Japan.
FAU - Fukasawa, Y
AU  - Fukasawa Y
FAU - Miyamoto, K
AU  - Miyamoto K
FAU - Takeda, E
AU  - Takeda E
FAU - Endou, H
AU  - Endou H
FAU - Kanai, Y
AU  - Kanai Y
LA  - eng
SI  - GENBANK/AB024400
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Amino Acid Transport Systems)
RN  - 0 (Amino Acids)
RN  - 0 (Antigens, CD)
RN  - 0 (Carrier Proteins)
RN  - 0 (Fusion Regulatory Protein-1)
RN  - 0 (Membrane Proteins)
RN  - 0 (RNA, Complementary)
RN  - 0 (RNA, Messenger)
RN  - GMW67QNF9C (Leucine)
SB  - IM
SB  - S
MH  - Amino Acid Sequence
MH  - Amino Acid Transport Systems
MH  - Amino Acids/metabolism
MH  - Animals
MH  - Antigens, CD/genetics
MH  - Biological Transport
MH  - Carrier Proteins/chemistry/*genetics
MH  - Cloning, Molecular
MH  - Fusion Regulatory Protein-1
MH  - Hydrogen-Ion Concentration
MH  - Intestine, Small/*metabolism
MH  - Kinetics
MH  - Leucine/metabolism
MH  - Membrane Proteins/chemistry/genetics
MH  - Molecular Sequence Data
MH  - Oocytes/metabolism
MH  - RNA, Complementary/genetics
MH  - RNA, Messenger/metabolism
MH  - Rats
MH  - Sequence Alignment
MH  - Substrate Specificity
MH  - Xenopus
EDAT- 1999/07/03 00:00
MHDA- 1999/07/03 00:01
CRDT- 1999/07/03 00:00
PHST- 1999/07/03 00:00 [pubmed]
PHST- 1999/07/03 00:01 [medline]
PHST- 1999/07/03 00:00 [entrez]
AID - 10.1074/jbc.274.28.19745 [doi]
PST - ppublish
SO  - J Biol Chem. 1999 Jul 9;274(28):19745-51. doi: 10.1074/jbc.274.28.19745.