Proximal signaling events in the TCR-coupled signaling pathway. Interactions between the TCR and peptide-MHC results in the activation of Lck, a member of the Src family of tyrosine kinases. Lck then phosphorylates the two-tyrosine residues within the ITAMs of the CD3 and ζ chains. A second tyrosine kinase, ZAP-70, is specifically recruited to biphosphorylated ITAMs. Phosphorylation of ZAP-70 by Lck results in its activation. ZAP-70 and Lck phosphorylate and activate several downstream target proteins eventually leading to Ras activation, calcium mobilization, and actin cytoskeleton rearrangements, and ultimately to the activation of transcription factors.