title: Regulation of Lck activity by CD4 and CD28 in the immunological synapse.
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.
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, 660 S. Euclid, Campus Box 8118, St. Louis, MO 63110, USA.
authors.forename: Amy D
authors.initials: AD
authors.lastname: Holdorf
authors.forename: Kyeong-Hee
authors.initials: KH
authors.lastname: Lee
authors.forename: W Richard
authors.initials: WR
authors.lastname: Burack
authors.forename: Paul M
authors.initials: PM
authors.lastname: Allen
authors.forename: Andrey S
authors.initials: AS
authors.lastname: Shaw
mesh_terms: D000818:Animals; D018106:CD28 Antigens / Q000502:physiology*; D015704:CD4 Antigens / Q000502:physiology*; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D010766:Phosphorylation; D011817:Rabbits; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D013569:Synapses / Q000201:enzymology*
chemical_list: D018106:CD28 Antigens; D015704:CD4 Antigens; D011948:Receptors, Antigen, T-Cell; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)