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Gene Review

LAT  -  linker for activation of T cells

Homo sapiens

Synonyms: 36 kDa phospho-tyrosine adapter protein, LAT1, Linker for activation of T-cells family member 1, p36-38, pp36
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Disease relevance of LAT


Psychiatry related information on LAT


High impact information on LAT

  • Using a two color imaging approach that allows tracking of single molecules relative to the CD2/LAT/Lck clusters, we demonstrate that these microdomains exclude and limit the free diffusion of molecules in the membrane but also can trap and immobilize specific proteins [7].
  • These microdomains require protein-protein interactions mediated through phosphorylation of LAT and are not maintained by interactions with actin or lipid rafts [7].
  • LAT: the ZAP-70 tyrosine kinase substrate that links T cell receptor to cellular activation [8].
  • Therefore, we propose to name the molecule LAT-linker for activation of T cells [8].
  • By similar criteria, we determine that lipocortin II is the human analogue of pp36, a major substrate for pp60src, which has been characterized in chicken embryo fibroblasts and in bovine brush border preparations [9].

Chemical compound and disease context of LAT


Biological context of LAT


Anatomical context of LAT


Associations of LAT with chemical compounds


Physical interactions of LAT

  • Incidentally, Grf40 binds to linker for activation of T cells (LAT) possibly via its SH2 domain [23].
  • Phosphorylated LAT binds Grb2, PLC-gamma1, and other signaling molecules [24].
  • Taken together, these results suggest that, unlike the non-raft pool, CD38 in rafts is able to initiate and propagate several activating signaling pathways, possibly by facilitating critical associations within other raft subsets, for example, LAT rafts via its capacity to interact with Lck and CD3-zeta [25].

Enzymatic interactions of LAT


Regulatory relationships of LAT


Other interactions of LAT


Analytical, diagnostic and therapeutic context of LAT


  1. The adaptor molecules LAT and SLP-76 are specifically targeted by Yersinia to inhibit T cell activation. Gerke, C., Falkow, S., Chien, Y.H. J. Exp. Med. (2005) [Pubmed]
  2. In situ expression of LAT (linker for activation of T cells) in pathological human skin with T-lymphoid infiltrate. Alaibac, M., Pigozzi, B., Fortina, A.B., Michelotto, G., Peserico, A. Arch. Dermatol. Res. (2004) [Pubmed]
  3. Role of the LAT adaptor in T-cell development and Th2 differentiation. Malissen, B., Aguado, E., Malissen, M. Adv. Immunol. (2005) [Pubmed]
  4. ZAP-70 expression in normal pro/pre B cells, mature B cells, and in B-cell acute lymphoblastic leukemia. Crespo, M., Villamor, N., Giné, E., Muntañola, A., Colomer, D., Marafioti, T., Jones, M., Camós, M., Campo, E., Montserrat, E., Bosch, F. Clin. Cancer Res. (2006) [Pubmed]
  5. Human immunodeficiency virus type 1 Nef associates with lipid rafts to downmodulate cell surface CD4 and class I major histocompatibility complex expression and to increase viral infectivity. Alexander, M., Bor, Y.C., Ravichandran, K.S., Hammarskjöld, M.L., Rekosh, D. J. Virol. (2004) [Pubmed]
  6. LAT1 gene variants-potential factors influencing the clinical course of phenylketonuria. Bik-Multanowski, M., Pietrzyk, J.J. J. Inherit. Metab. Dis. (2006) [Pubmed]
  7. Single-molecule microscopy reveals plasma membrane microdomains created by protein-protein networks that exclude or trap signaling molecules in T cells. Douglass, A.D., Vale, R.D. Cell (2005) [Pubmed]
  8. LAT: the ZAP-70 tyrosine kinase substrate that links T cell receptor to cellular activation. Zhang, W., Sloan-Lancaster, J., Kitchen, J., Trible, R.P., Samelson, L.E. Cell (1998) [Pubmed]
  9. Two human 35 kd inhibitors of phospholipase A2 are related to substrates of pp60v-src and of the epidermal growth factor receptor/kinase. Huang, K.S., Wallner, B.P., Mattaliano, R.J., Tizard, R., Burne, C., Frey, A., Hession, C., McGray, P., Sinclair, L.K., Chow, E.P. Cell (1986) [Pubmed]
  10. Trichostatin A down-regulates ZAP-70, LAT and SLP-76 content in Jurkat T cells. Januchowski, R., Jagodzinski, P.P. Int. Immunopharmacol. (2007) [Pubmed]
  11. Development of a latex agglutination test for rapid identification of Escherichia coli. Huang, Y.H., Chang, H.C., Chang, T.C. Eur. J. Clin. Microbiol. Infect. Dis. (2001) [Pubmed]
  12. Structural basis for differential recognition of tyrosine-phosphorylated sites in the linker for activation of T cells (LAT) by the adaptor Gads. Cho, S., Velikovsky, C.A., Swaminathan, C.P., Houtman, J.C., Samelson, L.E., Mariuzza, R.A. EMBO J. (2004) [Pubmed]
  13. The adapter protein LAT enhances fcgamma receptor-mediated signal transduction in myeloid cells. Tridandapani, S., Lyden, T.W., Smith, J.L., Carter, J.E., Coggeshall, K.M., Anderson, C.L. J. Biol. Chem. (2000) [Pubmed]
  14. Molecular cloning of a novel gene encoding a membrane-associated adaptor protein (LAX) in lymphocyte signaling. Zhu, M., Janssen, E., Leung, K., Zhang, W. J. Biol. Chem. (2002) [Pubmed]
  15. The hematopoietic-specific adaptor protein gads functions in T-cell signaling via interactions with the SLP-76 and LAT adaptors. Liu, S.K., Fang, N., Koretzky, G.A., McGlade, C.J. Curr. Biol. (1999) [Pubmed]
  16. Mechanisms of signaling by the hematopoietic-specific adaptor proteins, SLP-76 and LAT and their B cell counterpart, BLNK/SLP-65. Yablonski, D., Weiss, A. Adv. Immunol. (2001) [Pubmed]
  17. Non-T cell activation linker (NTAL): a transmembrane adaptor protein involved in immunoreceptor signaling. Brdicka, T., Imrich, M., Angelisová, P., Brdicková, N., Horváth, O., Spicka, J., Hilgert, I., Lusková, P., Dráber, P., Novák, P., Engels, N., Wienands, J., Simeoni, L., Osterreicher, J., Aguado, E., Malissen, M., Schraven, B., Horejsí, V. J. Exp. Med. (2002) [Pubmed]
  18. SLAP, a dimeric adapter protein, plays a functional role in T cell receptor signaling. Tang, J., Sawasdikosol, S., Chang, J.H., Burakoff, S.J. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  19. Synergistic assembly of linker for activation of T cells signaling protein complexes in T cell plasma membrane domains. Hartgroves, L.C., Lin, J., Langen, H., Zech, T., Weiss, A., Harder, T. J. Biol. Chem. (2003) [Pubmed]
  20. Association of Grb2, Gads, and phospholipase C-gamma 1 with phosphorylated LAT tyrosine residues. Effect of LAT tyrosine mutations on T cell angigen receptor-mediated signaling. Zhang, W., Trible, R.P., Zhu, M., Liu, S.K., McGlade, C.J., Samelson, L.E. J. Biol. Chem. (2000) [Pubmed]
  21. Dynamic changes in the mobility of LAT in aggregated lipid rafts upon T cell activation. Tanimura, N., Nagafuku, M., Minaki, Y., Umeda, Y., Hayashi, F., Sakakura, J., Kato, A., Liddicoat, D.R., Ogata, M., Hamaoka, T., Kosugi, A. J. Cell Biol. (2003) [Pubmed]
  22. Effect of redox balance alterations on cellular localization of LAT and downstream T-cell receptor signaling pathways. Gringhuis, S.I., Papendrecht-van der Voort, E.A., Leow, A., Nivine Levarht, E.W., Breedveld, F.C., Verweij, C.L. Mol. Cell. Biol. (2002) [Pubmed]
  23. Grf40, A novel Grb2 family member, is involved in T cell signaling through interaction with SLP-76 and LAT. Asada, H., Ishii, N., Sasaki, Y., Endo, K., Kasai, H., Tanaka, N., Takeshita, T., Tsuchiya, S., Konno, T., Sugamura, K. J. Exp. Med. (1999) [Pubmed]
  24. LAT palmitoylation: its essential role in membrane microdomain targeting and tyrosine phosphorylation during T cell activation. Zhang, W., Trible, R.P., Samelson, L.E. Immunity (1998) [Pubmed]
  25. CD38 signaling in T cells is initiated within a subset of membrane rafts containing Lck and the CD3-zeta subunit of the T cell antigen receptor. Muñoz, P., Navarro, M.D., Pavón, E.J., Salmerón, J., Malavasi, F., Sancho, J., Zubiaur, M. J. Biol. Chem. (2003) [Pubmed]
  26. T-cell antigen receptor-induced signaling complexes: internalization via a cholesterol-dependent endocytic pathway. Barr, V.A., Balagopalan, L., Barda-Saad, M., Polishchuk, R., Boukari, H., Bunnell, S.C., Bernot, K.M., Toda, Y., Nossal, R., Samelson, L.E. Traffic (2006) [Pubmed]
  27. LAT displacement from lipid rafts as a molecular mechanism for the inhibition of T cell signaling by polyunsaturated fatty acids. Zeyda, M., Staffler, G., Horejsi, V., Waldhausl, W., Stulnig, T.M. J. Biol. Chem. (2002) [Pubmed]
  28. Mapping the Zap-70 phosphorylation sites on LAT (linker for activation of T cells) required for recruitment and activation of signalling proteins in T cells. Paz, P.E., Wang, S., Clarke, H., Lu, X., Stokoe, D., Abo, A. Biochem. J. (2001) [Pubmed]
  29. Dynamic molecular interactions linking the T cell antigen receptor to the actin cytoskeleton. Barda-Saad, M., Braiman, A., Titerence, R., Bunnell, S.C., Barr, V.A., Samelson, L.E. Nat. Immunol. (2005) [Pubmed]
  30. CD28 ligation induces rapid tyrosine phosphorylation of the linker molecule LAT in the absence of Syk and ZAP-70 tyrosine phosphorylation. Tsuchida, M., Manthei, E.R., Knechtle, S.J., Hamawy, M.M. Eur. J. Immunol. (1999) [Pubmed]
  31. Protein tyrosine phosphatase CD148-mediated inhibition of T-cell receptor signal transduction is associated with reduced LAT and phospholipase Cgamma1 phosphorylation. Baker, J.E., Majeti, R., Tangye, S.G., Weiss, A. Mol. Cell. Biol. (2001) [Pubmed]
  32. Signaling via LAT (linker for T-cell activation) and Syk/ZAP70 is required for ERK activation and NFAT transcriptional activation following CD2 stimulation. Martelli, M.P., Lin, H., Zhang, W., Samelson, L.E., Bierer, B.E. Blood (2000) [Pubmed]
  33. The importance of three membrane-distal tyrosines in the adaptor protein NTAL/LAB. Koonpaew, S., Janssen, E., Zhu, M., Zhang, W. J. Biol. Chem. (2004) [Pubmed]
  34. 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]
  35. Chromosomal localization and genomic organization of the human Linker for Activation of T cells (LAT) gene. Windpassinger, C., Kroisel, P.M., Wagner, K., Petek, E. Cytogenet. Genome Res. (2002) [Pubmed]
  36. Increased ubiquitination and reduced expression of LCK in T lymphocytes from patients with systemic lupus erythematosus. Jury, E.C., Kabouridis, P.S., Abba, A., Mageed, R.A., Isenberg, D.A. Arthritis Rheum. (2003) [Pubmed]
  37. Studying multisite binary and ternary protein interactions by global analysis of isothermal titration calorimetry data in SEDPHAT: Application to adaptor protein complexes in cell signaling. Houtman, J.C., Brown, P.H., Bowden, B., Yamaguchi, H., Appella, E., Samelson, L.E., Schuck, P. Protein Sci. (2007) [Pubmed]
  38. T cell activation-dependent association between the p85 subunit of the phosphatidylinositol 3-kinase and Grb2/phospholipase C-gamma 1-binding phosphotyrosyl protein pp36/38. Fukazawa, T., Reedquist, K.A., Panchamoorthy, G., Soltoff, S., Trub, T., Druker, B., Cantley, L., Shoelson, S.E., Band, H. J. Biol. Chem. (1995) [Pubmed]
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