Proposed model for the regulation of NFAT activity by SHP-1.

Inhibition of constitutive SHP-1 activity by bpV molecules triggers a series of biochemical events characteristic of the early steps of TCR signaling. As such, the inhibition of SHP-1 leads to the initiation of a cascade through the sudden activation of ZAP-70 and p56^lck, 2 well-known substrates of SHP-1. From these activated PTKs, a typical TCR-like downstream cascade of events would then induce NFAT-dependent transcriptional activity through the activation of both the Vav/SLP76 and Ras/Raf pathways, which culminate in activation of the AP-1 factor. In parallel, capacitance calcium entry would also be turned on through both the CRAC ion pump and the ZAP-70–dependent intracellular calcium release. The concomitant activation of both NFAT and AP-1 would then lead to the transcriptional induction of the IL-2 gene as well as the HIV-1 LTR (although this latter probably does not necessitate the presence of AP-1).