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  • Title: Regulation of Lck activity by CD4 and CD28 in the immunological synapse.
    Author: Holdorf AD, Lee KH, Burack WR, Allen PM, Shaw AS.
    Journal: Nat Immunol; 2002 Mar; 3(3):259-64. PubMed ID: 11828322.
    Abstract:
    Although the Src family tyrosine kinase Lck is essential for T cell receptor (TCR) signaling, whether or how Lck is activated is unknown. Using a phosphospecific antiserum to Lck, we show here that Lck becomes autophosphorylated when T cells are stimulated by antigen-presenting cells (APCs). We found that TCR cross-linking alone could not stimulate Lck autophosphorylation and CD45 was not required for this process. Instead, the T cell accessory molecules CD4 and CD28 cooperated to induce autophosphorylation of Lck. CD4 recruited Lck to the T cell--APC interface, whereas CD28 sustained Lck activation. These data show how the multiple interactions afforded by the immunological synapse drive efficient and highly specific signaling.
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