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Gene Review:

Lat - linker for activation of T cells

Mus musculus

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

Fukazawa, T. et al., Ardouin, L. et al., Wang, Y. et al., van Oers, N.S. et al., Ralston, R. et al.

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Disease relevance of Lat

We showed that Pax5(-/-) Lat(-/-) pro-B cell lines can be infected with recombinant retroviruses expressing a LAT cDNA and sorted for the expression of LAT [1].

High impact information on Lat

The time-course and dose-response for this modification of pp60c-src paralleled PDGF-induced increases in phosphorylation of pp36, a major cellular substrate for several tyrosine-specific protein kinases [2].
To delineate their roles in B-cell development and function, Ntal-deficient mice were generated and crossed with Lat-deficient mice [3].
Regardless of the number of TCR-zeta ITAMs present in the TCR complex, we report that a number of molecules involved in downstream signaling events, such as ZAP-70, SLP-76, and pp36, are all inducibly tyrosine phosphorylated following TCR ligation [4].
Association of pp36/38 with PI-3-K p85 was confirmed by transfection of a hemagglutinin-tagged p85 alpha cDNA into Jurkat cells followed by anti-hemagglutinin immunoprecipitation [5].
In vitro binding experiments with glutathione S-transferase fusion proteins of PI-3-K p85 demonstrated that the SH2 domains, but not the SH3 domain, mediated binding to pp36/38 [5].

Anatomical context of Lat

B cells developed in Lat(-/-) Ntal(-/-) double-deficient mice and in mice lacking either of the two adaptors with the same efficiency as in wild-type mice [3].
Considering that the handling of Pax5(-/-) pro-B cell lines is easier than that of bone marrow hematopoietic precursors, we used them for the rapid functional analysis of a novel Lat allelic series [1].
The tyrosine-phosphorylated form of pp36/38 is membrane-associated and directly interacts with phospholipase C-gamma 1 and Grb2, providing one mechanism to recruit downstream effectors to the cell membrane [5].
Here, we demonstrate that in Jurkat T cells, pp36/38 associates with the p85 subunit of phosphatidylinositol 3-kinase (PI-3-K p85) in an activation-dependent manner [5].

Other interactions of Lat

Rapid in vivo analysis of mutant forms of the LAT adaptor using Pax5-Lat double-deficient pro-B cells [1].

References

Rapid in vivo analysis of mutant forms of the LAT adaptor using Pax5-Lat double-deficient pro-B cells. Ardouin, L., Rolink, A.G., Mura, A.M., Gommeaux, J., Melchers, F., Busslinger, M., Malissen, M., Malissen, B. Eur. J. Immunol. (2005) [Pubmed]
The product of the protooncogene c-src is modified during the cellular response to platelet-derived growth factor. Ralston, R., Bishop, J.M. Proc. Natl. Acad. Sci. U.S.A. (1985) [Pubmed]
Single and combined deletions of the NTAL/LAB and LAT adaptors minimally affect B-cell development and function. Wang, Y., Horvath, O., Hamm-Baarke, A., Richelme, M., Grégoire, C., Guinamard, R., Horejsi, V., Angelisova, P., Spicka, J., Schraven, B., Malissen, B., Malissen, M. Mol. Cell. Biol. (2005) [Pubmed]
Regulation of TCR signal transduction in murine thymocytes by multiple TCR zeta-chain signaling motifs. van Oers, N.S., Love, P.E., Shores, E.W., Weiss, A. J. Immunol. (1998) [Pubmed]
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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