Figure 3.

GPI-anchored PrP^C has the capacity to interact with multiple partners and trigger cell signaling events leading to neuroprotection and immunomodulation. The formation of PrP^C-containing multimolecular complexes and subsequent mobilization of protective or immunomodulatory signals may be induced following the binding of soluble ligands, such as STI1, PrP^C itself, or its N-terminal domain (PrP-N1). (A) In neurons, several targets of PrP^C signaling relay its neuroprotective action, including protein kinase A, mTOR, the MAP kinases ERK1/2, and GSK3b. This action may also involve intracellular calcium mobilization. Some of these signaling cascades require the association of PrP^C with the membrane protein caveolin. The participation of transmembrane partner(s) of PrP^C to the signaling complexes is represented by «β». (B) In T lymphocytes, PrP^C is enriched at the immunological synapse, where it can interact with components of the T cell receptor (TCR), such as the Fyn tyrosine kinase and the zeta chain-associated protein kinase 70 (ZAP-70). These interactions may further promote the activation of downstream effectors, including NFkB, JNK, ERK, as well as elevation of intracellular calcium concentration.