The tyrosine protein kinase p56ick transduces signals important for antigen-induced T-cell The lymphocyte-specific tyrosine protein kinase, p561ck, is expressed predominantly in T cells (13,30,53), where it is physically associated with the T-cell transmembrane proteins CD4 and CD8 (43,45,52). During T-cell activation, CD4 and CD8 bind to the major histocompatibility complex glycoprotein (class II or class I, respectively) on an antigen-presenting cell, bringing p56ick in close physical proximity to the T-cell receptor (16). Binding of the antigen-major histocompatibility complex to CD4 and the T-cell receptor subunits triggers the rapid phosphorylation of a set of T-cell proteins on tyrosine (20). pS6ick is thought to mediate some of these phosphorylations, because the addition of antibodies that cross-link cell surface CD4 induces tyrosine phosphorylation of p56ick and activates its phosphotransferase activity in vitro (19, 27).Genetic evidence likewise indicates that enhancement of T-cell activation by CD4 is mediated through pS6Ick. Deletion of the cytoplasmic domain of CD4 that binds p56 ck abrogates the ability of CD4 to enhance antigen-induced interleukin 2 (IL-2) production in CD4-dependent cells (18,33,46), and T cells expressing activated p56Ik are hypersensitive to stimulation through the T-cell receptor (1) while those lacking functional p56iCk are defective in inducing the transient increase in intracellular free calcium that accompanies antigenic stimulation through the T-cell receptor (48). Therefore, p56 Ck performs a pivotal role in T-cell activation.