Ask about this productRelated genes to: LAT2 antibody
- Gene:
- LAT2 NIH gene
- Name:
- linker for activation of T cells family member 2
- Previous symbol:
- WBSCR15, WBSCR5
- Synonyms:
- WSCR5, HSPC046, LAB, NTAL
- Chromosome:
- 7q11.23
- Locus Type:
- gene with protein product
- Date approved:
- 1997-09-12
- Date modifiied:
- 2017-12-06
- Gene:
- SLC7A8 NIH gene
- Name:
- solute carrier family 7 member 8
- Previous symbol:
- -
- Synonyms:
- LPI-PC1, LAT2
- Chromosome:
- 14q11.2
- Locus Type:
- gene with protein product
- Date approved:
- 1999-10-05
- Date modifiied:
- 2016-02-17
Related products to: LAT2 antibody
Related articles to: LAT2 antibody
- L-type amino acid transporters LAT1 (SLC7A5) and LAT2 (SLC7A8) facilitate the bidirectional transport of branched and aromatic amino acids (AAs) across the plasma membrane. LAT1 has emerged as a key therapeutic target in cancer due to its upregulation in different tumor types. We generated and characterized LAT1- and LAT2-expressing cells using the human MDST8 cell line lacking these transporters to evaluate the specificity and selectivity of the clinical candidate JPH203 and novel LAT1 inhibitors. Both LAT1 and LAT2 increased the expression of 4F2hc, a heavy chain protein essential for LAT1 functioning and AA transport. We show for the first time that two potent nanomolar LAT1 inhibitors, JPH203 and JX-078, can enter cells through LAT1-independent mechanisms and inhibit LAT1-mediated L-leucine efflux, giving rise to differential cell type and time-dependent effects on the AA metabolome and metabolic activity in cancer cells and human PBMCs. Intriguingly, the antiproliferative effects of JPH203 and JX-078 on MDST8 cells were LAT1-independent, showing also micromolar IC50 values in HT-29 and U937 cells that overexpress LAT1. We found notable differences in the bioavailability of LAT1 inhibitors in mice. Oral administration of JX-078 efficiently penetrated tissues and crossed the blood-brain barrier, leading to increased levels of inhibitory neurotransmitters glycine and GABA in the brain. This study demonstrates the utility of employing targeted metabolomics to interrogate LAT1/2 inhibitor selectivity in different physiological matrices in vitro, ex vivo and in vivo. Overall, our findings reveal LAT1-dependent and previously unrecognized LAT-independent effects of inhibitors believed to act specifically on LAT1. - Source: PubMed
Publication date: 2025/07/31
Morozova VeronikaPellegata DanieleSinger SimonCharles Roch-PhilippeMüller JenniferAltmann Karl-HeinzGertsch Jürg - The neutral amino acid transporter SLC7A8 (LAT2) has been described as a key regulator of metabolic adaptation. LAT2 mutations in human populations have been linked to the early onset of age-related hearing loss and cataract growth. As LAT2 was previously found to be highly expressed in skeletal muscle, here we characterised its role in the regulation of skeletal muscle amino acid flux and metabolic adaptation to fasting. - Source: PubMed
Espino-Guarch MeritxellHuang Susie Shih YinVilches ClaraPrat EstherEl Nahas RanaMissous GhaliaBodoy SusannaSathappan AbbiramiAl-Aghbar Mohammad AmeenMayayo ClaraOlivé MontseBusquets-Rius SilviaSebastián DavidZorzano AntonioPalacin Manuelvan Panhuys NicholasNunes Virginia - T helper 9 (Th9) cells are implicated in allergic skin inflammation and depend on the transcription factor peroxisome proliferator-activated receptor-γ (PPAR-γ) for full effector function. In this study, we uncovered a role for PPAR-γ in the amino acid metabolism of human Th9 cells. In in vitro-primed Th9 cells, PPAR-γ expression positively correlated with the expression of SLC7A8, which encodes LAT2, a transporter of large neutral amino acids, including cystine. Inhibition of PPAR-γ led to a compensatory upregulation of SLC7A11, a subunit of the cystine-glutamine antiporter xCT, indicating a specific need for cystine uptake in Th9 cells. Indeed, Th9 cells were sensitive to cystine deprivation, which triggered lipid peroxidation and bioenergetic failure, resulting in a ferroptosis-like form of cell death. This outcome was further enforced by additional PPAR-γ inhibition. Finally, combined SLC7A11 and PPAR-γ inhibition depleted Th9 cells in ex vivo samples of acute allergic skin inflammation. Overall, our data suggest that human Th9 cells are dependent on uptake of exogenous cystine, which opens up promising therapeutic strategies for their inhibition or depletion in allergic skin inflammation. - Source: PubMed
Publication date: 2024/12/24
Bazzini CeciliaBertschi Nicole LSteck OliverLuther FabianSchärli StefanieRolfes Eva DVallone AngelaBegré NadjaNuoffer Jean-MarcRadonijc-Hoesli SusanneSimon DagmarSchlapbach Christoph - Cholangiocarcinoma (CCA) is often diagnosed late, leading to incomplete tumor removal, drug resistance and reduced chemotherapy efficacy. Curcumin has the potential for anti-cancer activity through various therapeutic properties and can improve the efficacy of chemotherapy. We aimed to investigate the synergistic effect of a combination of curcumin and gemcitabine against CCA, targeting the LAT2/glutamine pathway. This combination synergistically suppressed proliferation in gemcitabine-resistant CCA cells (KKU-213B). It also resulted in a remarkable degree of CCA cell apoptosis and cell cycle arrest, characterized by a high proportion of cells in the S and G2/M phases. Knockdown of SLC7A8 decreased the expressions of glutaminase and glutamine synthetase, resulting in inhibited cell proliferation and sensitized CCA cells to gemcitabine treatment. Moreover, in vivo experiments showed that a combination curcumin and gemcitabine significantly reduced tumor size, tumor growth rate and LAT2 expression in a gemcitabine-resistant CCA xenograft mouse model. Suppression of tumor progression in an orthotopic CCA hamster model provided strong support for clinical application. In conclusion, curcumin synergistically enhances gemcitabine efficacy against gemcitabine-resistant CCA by induction of apoptosis, partly via inhibiting LAT2/glutamine pathway. This approach may be an alternative strategy for the treatment of gemcitabine-resistant in CCA patients. - Source: PubMed
Publication date: 2024/07/11
Thongpon PhonpilasIntuyod KittiChomwong SasitornPongking ThatsanapongKlungsaeng SirinaphaMuisuk KanhaCharoenram NaruecharSitthirach ChutimaThanan RaynooPinlaor PorntipPinlaor Somchai - Chronic kidney disease (CKD) and hypertension are chronic diseases affecting a large portion of the population frequently coexistent and interdependent. The inability to produce/use adequate renal dopamine may contribute to the development of hypertension and renal dysfunction. The heterodimeric amino acid transporter LAT2/4F2hc (SLC7A8/SLC3A2 genes) promotes the uptake of L-DOPA, the natural precursor of dopamine. We examined the plausibility that SLC7A8/SLC3A2 gene polymorphisms may contribute to hypertensive CKD by affecting the L-DOPA uptake. - Source: PubMed
Publication date: 2024/06/18
Crocco PaolinaDato SerenaLa Grotta RossellaPassarino GiuseppeRose Giuseppina