Regulation of Lck activity by CD4 and CD28 in the immunological synapse

Amy D. Holdorf, Kyeong Hee Lee, W. Richard Burack, Paul M. Allen, Andrey S. Shaw

Research output: Contribution to journalArticlepeer-review

181 Scopus citations


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.

Original languageEnglish
Pages (from-to)259-264
Number of pages6
JournalNature immunology
Issue number3
StatePublished - 2002


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