biostudies-literatureVarghese BNCI NIH HHS2356-65https://www.ebi.ac.uk/biostudies/studies/S-EPMC2999476biostudies-literatureUnknown24(12)Mitogenic and prosurvival effects underlie the tumorigenic roles of prolactin (PRL) in the pathogenesis of breast cancer. PRL signaling is mediated through its receptor (PRLr). A proteomics screen identified the pyruvate kinase M2 (PKM2), a glycolytic enzyme known to play an important role in tumorigenesis, as a protein that constitutively interacts with PRLr. Treatment of cells with PRL inhibited pyruvate kinase activity and increased the lactate content in human cells in a manner that was dependent on the abundance of PRLr, activation of Janus kinase 2, and tyrosine phosphorylation of the intracellular domain of PRLr. Knockdown of PKM2 attenuated PRL-stimulated cell proliferation. The extent of this proliferation was rescued by the knock-in of the wild-type PKM2 but not of its mutant insMolecular endocrinology (Baltimore, Md.)Prolactin inhibits activity of pyruvate kinase M2 to stimulate cell proliferation.PMC2999476R01 CA115281T32CA09140T32 CA009140R01 CA118740CA118740CA115281Swaminathan GRui HYang NTzimas CPlotnikov AFuchs SYVarghese BfalseProlactin inhibits activity of pyruvate kinase M2 to stimulate cell proliferation.Mitogenic and prosurvival effects underlie the tumorigenic roles of prolactin (PRL) in the pathogenesis of breast cancer. PRL signaling is mediated through its receptor (PRLr). A proteomics screen identified the pyruvate kinase M2 (PKM2), a glycolytic enzyme known to play an important role in tumorigenesis, as a protein that constitutively interacts with PRLr. Treatment of cells with PRL inhibited pyruvate kinase activity and increased the lactate content in human cells in a manner that was dependent on the abundance of PRLr, activation of Janus kinase 2, and tyrosine phosphorylation of the intracellular domain of PRLr. Knockdown of PKM2 attenuated PRL-stimulated cell proliferation. The extent of this proliferation was rescued by the knock-in of the wild-type PKM2 but not of its mutant ins2010-01-01T00:00:00Z2010 Dec2025-04-05T14:46:11.184Z2019-03-27T00:37:16ZS-EPMC29994762096204210.1210/me.2010-0219