Prolactin inhibits activity of pyruvate kinase M2 to stimulate cell proliferation. Mol Endocrinol 2010 Dec;24(12):2356-65
Date
10/22/2010Pubmed ID
20962042Pubmed Central ID
PMC2999476DOI
10.1210/me.2010-0219Scopus ID
2-s2.0-78649416447 (requires institutional sign-in at Scopus site) 26 CitationsAbstract
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 insensitive to PRL-mediated inhibition. We discuss a hypothesis that the inhibition of PKM2 by PRL contributes to the PRL-stimulated cell proliferation.
Author List
Varghese B, Swaminathan G, Plotnikov A, Tzimas C, Yang N, Rui H, Fuchs SYMESH terms used to index this publication - Major topics in bold
AnimalsBreast Neoplasms
Cell Growth Processes
Cell Line
Cell Line, Tumor
Gene Knock-In Techniques
Gene Knockdown Techniques
Humans
Janus Kinase 2
Lactic Acid
Phosphorylation
Prolactin
Pyruvate Kinase
Rats
Receptors, Prolactin
Signal Transduction
Tyrosine
