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Gene Review

LAT2  -  linker for activation of T cells family,...

Homo sapiens

Synonyms: HSPC046, LAB, Linker for activation of B-cells, Linker for activation of T-cells family member 2, Membrane-associated adapter molecule, ...
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Disease relevance of LAT2


High impact information on LAT2

  • Many molecules involved in positive signaling, including the FcRbeta subunit, the src kinase lyn, the cytosolic adapter Grb2, and the transmembrane adapters LAT and NTAL, are indeed also involved in negative signaling [4].
  • Mice with the Lat2 gene conditionally deleted from T cells also developed the autoimmune syndrome like Lat2(-/-) mice [5].
  • In T and mast cells, ITAM-dependent signals are integrated by critical scaffolding elements such as LAT (linker for activation of T cells) and NTAL (non-T-cell activation linker) [6].
  • Unlike the Fc epsilon RI response, SCF induced NTAL phosphorylation in the absence of detectable LAT phosphorylation [7].
  • Unexpectedly however, the ability of NTAL to induce calcium flux was not sufficient to promote pre-B cell differentiation, suggesting that the PLC-gamma binding motif has only partial effects on NTAL-mediated pre-BCR signaling [8].

Biological context of LAT2

  • By generating chimeric swap mutants, we identified the N terminus of NTAL as an inhibitory domain that prevents pre-B cell differentiation while allowing pre-BCR down-regulation and receptor-mediated calcium flux [8].
  • This insertion rendered NTAL capable of activating pre-BCR down-regulation and calcium flux [8].
  • Transport of a neurotoxicant by molecular mimicry: the methylmercury-L-cysteine complex is a substrate for human L-type large neutral amino acid transporter (LAT) 1 and LAT2 [9].
  • Carrier-mediated ornithine transport via the L-type amino acid transporter (LAT)1, LAT2, cationic amino acid transporter (CAT)-1, and y(+)LAT2 systems was evaluated by short interfering (si)RNA-mediated gene silencing [10].
  • The tissue distribution of LAT1 suggests that it is involved mainly in transporting amino acids into growing cells and across some endothelial/epithelial secretory barriers, whereas the localization of LAT2 indicates that it is mainly involved in the basolateral efflux step of transepithelial (re)absorptive amino acid transport [11].

Anatomical context of LAT2


Associations of LAT2 with chemical compounds

  • Identification of stereoselective transporters for S-nitroso-L-cysteine: role of LAT1 and LAT2 in biological activity of S-nitrosothiols [13].
  • In addition, [(3)H]methionine efflux was trans -stimulated by leucine and phenylalanine even in the presence of an inwardly directed methionine gradient, demonstrating concentrative transport by both LAT1 and LAT2 [9].
  • The present study aimed to examine the presence and define the role of 4F2hc, a glycoprotein associated with the LAT2 amino acid transporter, in L-DOPA handling by LLC-PK(1) cells [14].
  • In addition, low levels of NTAL are correlated with decreased and delayed mobilization of Ca(2+) after TREM-1 triggering [15].
  • By analyzing receptor-induced tyrosine phosphorylation patterns, we discovered that the ligation of TREM-1 leads to tyrosine phosphorylation of the non-T cell activation linker (NTAL; also called linker of activation in B cells or LAB) in a myelomonocytic cell line and primary human granulocytes [15].

Regulatory relationships of LAT2

  • LAT-mediated signaling events were enhanced in Lat2(-/-) T cells; however, they were suppressed in T cells that overexpressed LAB [5].

Other interactions of LAT2


Analytical, diagnostic and therapeutic context of LAT2


  1. Transmembrane adaptor molecules: a new category of lymphoid-cell markers. Tedoldi, S., Paterson, J.C., Hansmann, M.L., Natkunam, Y., Rüdiger, T., Angelisova, P., Du, M.Q., Roberton, H., Roncador, G., Sanchez, L., Pozzobon, M., Masir, N., Barry, R., Pileri, S., Mason, D.Y., Marafioti, T., Horejsí, V. Blood (2006) [Pubmed]
  2. Chromosomally encoded ampC-type beta-lactamase in a clinical isolate of Proteus mirabilis. Bret, L., Chanal-Claris, C., Sirot, D., Chaibi, E.B., Labia, R., Sirot, J. Antimicrob. Agents Chemother. (1998) [Pubmed]
  3. Divergent human and mouse orthologs of a novel gene (WBSCR15/Wbscr15) reside within the genomic interval commonly deleted in Williams syndrome. Doyle, J.L., DeSilva, U., Miller, W., Green, E.D. Cytogenet. Cell Genet. (2000) [Pubmed]
  4. Negative signaling in Fc receptor complexes. Daëron, M., Lesourne, R. Adv. Immunol. (2006) [Pubmed]
  5. Negative Regulation of T Cell Activation and Autoimmunity by the Transmembrane Adaptor Protein LAB. Zhu, M., Koonpaew, S., Liu, Y., Shen, S., Denning, T., Dzhagalov, I., Rhee, I., Zhang, W. Immunity (2006) [Pubmed]
  6. Multiplicity and plasticity of natural killer cell signaling pathways. Chiesa, S., Mingueneau, M., Fuseri, N., Malissen, B., Raulet, D.H., Malissen, M., Vivier, E., Tomasello, E. Blood (2006) [Pubmed]
  7. NTAL phosphorylation is a pivotal link between the signaling cascades leading to human mast cell degranulation following Kit activation and Fc epsilon RI aggregation. Tkaczyk, C., Horejsi, V., Iwaki, S., Draber, P., Samelson, L.E., Satterthwaite, A.B., Nahm, D.H., Metcalfe, D.D., Gilfillan, A.M. Blood (2004) [Pubmed]
  8. The N Terminus of the Non-T Cell Activation Linker (NTAL) Confers Inhibitory Effects on Pre-B Cell Differentiation. Herzog, S., Jumaa, H. J. Immunol. (2007) [Pubmed]
  9. Transport of a neurotoxicant by molecular mimicry: the methylmercury-L-cysteine complex is a substrate for human L-type large neutral amino acid transporter (LAT) 1 and LAT2. Simmons-Willis, T.A., Koh, A.S., Clarkson, T.W., Ballatori, N. Biochem. J. (2002) [Pubmed]
  10. Ornithine transport via cationic amino Acid transporter-1 is involved in ornithine cytotoxicity in retinal pigment epithelial cells. Kaneko, S., Ando, A., Okuda-Ashitaka, E., Maeda, M., Furuta, K., Suzuki, M., Matsumura, M., Ito, S. Invest. Ophthalmol. Vis. Sci. (2007) [Pubmed]
  11. System L: heteromeric exchangers of large, neutral amino acids involved in directional transport. Verrey, F. Pflugers Arch. (2003) [Pubmed]
  12. Expression of LAT1 and LAT2 amino acid transporters in human and rat intestinal epithelial cells. Fraga, S., Pinho, M.J., Soares-da-Silva, P. Amino Acids (2005) [Pubmed]
  13. Identification of stereoselective transporters for S-nitroso-L-cysteine: role of LAT1 and LAT2 in biological activity of S-nitrosothiols. Li, S., Whorton, A.R. J. Biol. Chem. (2005) [Pubmed]
  14. Apical and basolateral 4F2hc and the amino acid exchange of L-DOPA in renal LLC-PK(1) cells. Soares-da-Silva, P., Serrão, M.P. Amino Acids (2005) [Pubmed]
  15. Non-T Cell Activation Linker (NTAL) Negatively Regulates TREM-1/DAP12-Induced Inflammatory Cytokine Production in Myeloid Cells. Tessarz, A.S., Weiler, S., Zanzinger, K., Angelisová, P., Horejsí, V., Cerwenka, A. J. Immunol. (2007) [Pubmed]
  16. Expression and adaptive regulation of amino acid transport system A in a placental cell line under amino acid restriction. Jones, H.N., Ashworth, C.J., Page, K.R., McArdle, H.J. Reproduction (2006) [Pubmed]
  17. Williams-Beuren syndrome critical region-5/non-T-cell activation linker: a novel target gene of AML1/ETO. Fliegauf, M., Stock, M., Berg, T., Lübbert, M. Oncogene (2004) [Pubmed]
  18. Identification and functional characterization of a Na(+)-independent large neutral amino acid transporter (LAT2) on ARPE-19 cells. Gandhi, M.D., Pal, D., Mitra, A.K. International journal of pharmaceutics. (2004) [Pubmed]
  19. An amino acid transporter involved in gastric acid secretion. Kirchhoff, P., Dave, M.H., Remy, C., Kosiek, O., Busque, S.M., Dufner, M., Geibel, J.P., Verrey, F., Wagner, C.A. Pflugers Arch. (2006) [Pubmed]
  20. Reabsorption of neutral amino acids mediated by amino acid transporter LAT2 and TAT1 in the basolateral membrane of proximal tubule. Park, S.Y., Kim, J.K., Kim, I.J., Choi, B.K., Jung, K.Y., Lee, S., Park, K.J., Chairoungdua, A., Kanai, Y., Endou, H., Kim, d.o. .K. Arch. Pharm. Res. (2005) [Pubmed]
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