PRLR ligands:p(Y611)-PRLR:p(Y1007)-JAK2 dimer:SHP2 PRLR ligands:p(Y611)-PRLR:p(Y1007)-JAK2 dimer:p-SHP2 SHP2 is phosphorylated Authored: Jupe, S, 2011-06-13 EC Number: 2.7.10.2 Edited: Jupe, S, 2011-10-17 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). Pubmed10991949 Pubmed8598196 Pubmed8943354 Pubmed9009077 Pubmed9062191 Pubmed9756938 Reactome Database ID Release 431369115 Reactome, http://www.reactome.org ReactomeREACT_115719 Reviewed: Goffin, V, 2011-11-08