Prolactin stimulation leads to tyrosine phosphorylation of the C-terminal SH2 domain of Shp2 and requires Jak2. This appears to be a positive regulatory influence on Prlr signaling. Shp2 interacts with a number of cellular proteins 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 members of the Gab (Grb2 associated binder) family, adaptor proteins that link activated receptor tyrosine kinase and cytokine receptors to downstream signaling molecules. PRL stimulation has been observed to lead to Gab2 asociation with SHP2 and the p85 subunit of PI3K, and Gab2 tyrosine phosphorylation, though it is not clear that SHP2 serves as a link between Prlr and Gab2 (Ali & Ali 2000).