Latching on to LAT

Science's STKE  07 Aug 2001:
Vol. 2001, Issue 94, pp. tw3
DOI: 10.1126/stke.2001.94.tw3

Full signaling from the T cell receptor (TCR) requires the presence of the linker for activation of T cells (LAT) protein. Human LAT contains 10 tyrosine residues, of which at least five reside in appropriate amino acid sequence contexts that may associate with phosphotyrosine-binding proteins. Lin and Weiss identified the tyrosine residues on LAT required for proper TCR-dependent calcium mobilization and mitogen-associated protein kinase (MAPK) activation. Tyr132, Tyr171, and Tyr191 together were responsible for mediating normal amounts of calcium flux; the presence of one, but not all, of these tyrosines drastically reduced calcium mobilization. Full MAPK activation required the presence of Tyr110 and Tyr226. In addition, Lin and Weiss found that full MAPK and calcium activation required the critical tyrosine residues to be fully present on individual LAT proteins; mutant LAT proteins containing some, but not all, of the essential tyrosines could not activate MAPK or calcium responses. Thus, although TCR-associated proteins may cluster into high-density complexes at the immune synapses, these results suggest that individual LAT molecules act as a hub for the binding of several critical TCR-dependent signaling proteins.

J. Lin, A. Weiss, Identification of the minimal tyrosine residues required for linker for activation of T cell function. J. Biol. Chem. 276, 29588-29595 (2001). [Abstract] [Full Text]