Meta-Biol

• Pathways

Prolactin stimulation leads to tyrosine phosphorylation of the C-terminal SH2 domain of SHP2 and requires JAK2 (Ali et al. 1996). This has a positive regulatory influence on PRLR signaling. SHP2 has a number of signaling-capable interactors such as signal regulatory proteins (SIRPs, Kharitonenkov et al. 1997), SH2-containing inositol phosphatase (SHIP, Liu et al. 1997), insulin receptor substrates 1 and 2 (Myers et al. 1998), JAK2 (Jiao et al. 1996) and GRB2 associated binder 2 (GAB2) an adaptor protein that links activated receptor tyrosine kinase and cytokine receptors to downstream signaling molecules. PRL stimulation leads to SHP2-GAB2 association, GAB2 tyrosine phosphorylation, and GAB2-PI3K p85 subunit association, though it is not clear that this is the order of events, nor that SHP2 serves as a link between PRLR and GAB2 (Ali & Ali 2000).