Fig 1.

Phosphorylation of ZAP-70 is required to initiate T cell receptor signaling. TCR signaling is initiated by two tyrosine kinases: the Src family kinase Lck and ZAP-70. Activated Lck phosphorylates ITAMs in the intracellular tails of ζ chains of the TCR complex. Doubly phosphorylated ITAMs recruit ZAP-70 from the cytosol to the plasma membrane. Tyr 315, Tyr 319, and Tyr 493 of ZAP-70 are phosphorylated by Lck to fully activate ZAP-70, enabling ZAP-70 to phosphorylate two scaffold proteins, LAT and SLP-76, leading to the recruitment of effector proteins that stimulate T cell activation.