Fig. 7. Signaling pathway outcomes involving PIRB and HACS1.

(a) Experimental evidence to date places PIRB in an antagonistic role towards several kinds of positive receptor signals, including those from B cell antigen receptor (BCR). Antagonism is achieved by the binding of SHP1 phosphatase to phosphorylated ITIMs, that in turn, prevent critical phosphorylations on BCR by kinases including Syk. The SHP1-PIRB relationship also antagonizes pathways associated with neuronal plasticity. (b) A similar representation of BCR and PIRB signaling that incorporates the HACS1 relationship presented in this study. If HACS1 can either displace or compete with SHP1 for binding PIRB, Syk may remain activated thereby enabling enhanced BCR signaling and neuronal plasticity. In its adaptor role, HACS1 can bring a different set of regulatory and signaling proteins to PIRB.