FIG. 7.

Hypothetical model of the ZAP-70 activation process. Lck phosphorylates ITAMs of activated TCR. ZAP-70 is recruited to phosphorylated ITAMs and subsequently phosphorylated by Lck on interdomain B tyrosines 315 and 319. This leads to a structural rearrangement of ZAP-70 molecule leading to increased accessibility of the activation loop and/or elevated kinase activity. This is followed by autophosphorylation of the activation loop, possibly via the coordinated action of Lck and ZAP-70 itself, and results in fully active ZAP-70 kinase. For simplicity, only Lck is shown in the model, but involvement of other PTKs should also be considered, as discussed in the text.