Evidence for two Types of Mediation of Neutral Amino-Acid Transport in Ehrlich Cells

Oxender, Dale L.; Christensen, Halvor N.

doi:10.1038/197765a0

Cited by 139 publications

(83 citation statements)

References 3 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The molecular nature of system A has not been determined yet. System L has been described originally as a transport agency responsible for the transport of large neutral amino acids with branched or aromatic side chains (1,7,8). Various subtypes with different characteristics in substrate selectivity and transport property have, however, been described so far for system L (9 -14).…”

Section: 32437-32445) Lat-2 Is a Nonglycosylated Membrane Protementioning

confidence: 99%

Identification and Functional Characterization of a Na+-independent Neutral Amino Acid Transporter with Broad Substrate Selectivity

Segawa¹,

Fukasawa²,

Miyamoto³

et al. 1999

Journal of Biological Chemistry

455

435

View full text Add to dashboard Cite

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 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 ␣-amino acids. LAT-2 exhibits higher affinity (K m ‫؍‬ 30 -50 M) to Tyr, Phe, Trp, Thr, Asn, Ile, Cys, Ser, Leu, Val, and Gln and relatively lower affinity (K m ‫؍‬ 180 -300 M) 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 K m value without changing the V max 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.

show abstract

Section: 32437-32445) Lat-2 Is a Nonglycosylated Membrane Protementioning

confidence: 99%

Identification and Functional Characterization of a Na+-independent Neutral Amino Acid Transporter with Broad Substrate Selectivity

Segawa¹,

Fukasawa²,

Miyamoto³

et al. 1999

Journal of Biological Chemistry

455

435

View full text Add to dashboard Cite

show abstract

“…Among amino acid transporters, system L is a Na þ -independent large and neutral amino acid transport agency (Oxender and Christensen, 1962;Christensen, 1990). L-type amino acid transporter 1 (LAT1) is one of the L-type amino acid transporters, and transports large neutral amino acids such as leucine, isoleucine, valine, phenylalanine, tyrosine, tryptophan, methionine and histidine (Oxender and Christensen, 1962;Kanai et al, 1998;Yanagida et al, 2001). L-type amino acid transporter 1 requires covalent association with the heavy chain of 4F2 cell surface antigen (4F2hc) for its functional expression in plasma membrane (Oxender and Christensen, 1962).…”

mentioning

confidence: 99%

“…L-type amino acid transporter 1 (LAT1) is one of the L-type amino acid transporters, and transports large neutral amino acids such as leucine, isoleucine, valine, phenylalanine, tyrosine, tryptophan, methionine and histidine (Oxender and Christensen, 1962;Kanai et al, 1998;Yanagida et al, 2001). L-type amino acid transporter 1 requires covalent association with the heavy chain of 4F2 cell surface antigen (4F2hc) for its functional expression in plasma membrane (Oxender and Christensen, 1962). Previous studies have shown LAT1 to be highly expressed in proliferating tissues, many tumour cell lines (T24 bladder carcinoma cells, RERF-LC-MA lung small-cell carcinoma cells, and HeLa uterine cervical carcinoma cells) and primary human tumours (Yanagida et al, 2001).…”

mentioning

confidence: 99%

Prognostic significance of L-type amino acid transporter 1 expression in resectable stage I–III nonsmall cell lung cancer

et al. 2008

View full text Add to dashboard Cite

The clinical significance of L-type amino acid transporter 1 (LAT1) expression remains unclear, whereas many experimental studies have demonstrated that LAT1 is associated with the proliferation of cancer cells. The purpose of this study was to evaluate the prognostic value of LAT1 in patients with nonsmall cell lung cancer (NSCLC). A total of 321 consecutive patients with completely resected pathologic stage I -III NSCLC were retrospectively reviewed. Expression of LAT1 and proliferative activity, as determined by the Ki-67 labelling index, was also evaluated immunohistochemically and correlated with the prognosis of patients who underwent complete resection of the tumour. Expression of LAT1 was positive in 163 patients (51%) (29% of adenocaricnoma (58 of 200 patients), 91% of squamous cell carcinoma (91 of 100 patients), and 67% of large cell carcinoma (14 of 21 patients)). The 5-year survival rate of LAT1-positive patients (51.8%) was significantly worse than that of LAT1-negative patients (87.8%; Po0.001). L-type amino acid transporter 1 expression was significantly associated with lymph node metastasis and disease stage. Multivariate analysis confirmed that positive expression of LAT1 was an independent factor for predicting a poor prognosis. There was a significant correlation between LAT1 expression and Ki-67 labelling index. LAT1 expression is a promising pathological factor to predict the prognosis in patients with resectable stage I -III NSCLC.

show abstract

“…System L, an amino acid transport system that mediates the Na-independent transport of large neural amino acid, was first described in Erhlich ascites tumor cells as an Na-independent system for neutral amino acids, which are inhibited by 2-aminobicyclo [2.2.1] heptane-2-carboxylic acid (BCH) [3,4,18,19,27]. System L also plays a pivotal role in the permeation of amino acids through blood-tissue barriers, such as the blood-brain and placenta barriers [4].…”

mentioning

confidence: 99%

Canine Lat1: Molecular Structure, Distribution and Its Expression in Cancer Samples

Ochiai

Morishita

Onda

et al. 2012

The Journal of Veterinary Medical Science

View full text Add to dashboard Cite

ABSTRACT. A full-length cDNA sequence of canine L-type amino acid transporter 1 (Lat1) was determined from a canine brain. The sequence was 1828 bp long and was predicted to encode 485 amino acid polypeptides. The deduced amino acid sequence of canine Lat1 showed 93.2% and 91.1% similarities to those of humans and rats, respectively. Northern blot analysis detected Lat1 expression in the cerebellum at 4 kb, and Western blot analysis showed a single band at 40 kDa. RT-PCR analysis revealed a distinct expression of Lat1 in the pancreas and testis in addition to the cerebrum and cerebellum. Notably, Lat1 expression was observed in the tissues of thyroid cancer, melanoma and hemangiopericytoma. Although the cancer samples examined were not enough, Lat1 may serve as a useful biomarker of cancer cells in veterinary clinic.

show abstract

Evidence for two Types of Mediation of Neutral Amino-Acid Transport in Ehrlich Cells

Cited by 139 publications

References 3 publications

Identification and Functional Characterization of a Na+-independent Neutral Amino Acid Transporter with Broad Substrate Selectivity

Identification and Functional Characterization of a Na+-independent Neutral Amino Acid Transporter with Broad Substrate Selectivity

Prognostic significance of L-type amino acid transporter 1 expression in resectable stage I–III nonsmall cell lung cancer

Canine Lat1: Molecular Structure, Distribution and Its Expression in Cancer Samples

Contact Info

Product

Resources

About