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Prolactin inhibits activity of pyruvate kinase M2 to stimulate cell proliferation.


ABSTRACT: 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.

SUBMITTER: Varghese B 

PROVIDER: S-EPMC2999476 | biostudies-other | 2010 Dec

REPOSITORIES: biostudies-other

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Prolactin inhibits activity of pyruvate kinase M2 to stimulate cell proliferation.

Varghese Bentley B   Swaminathan Gayathri G   Plotnikov Alexander A   Tzimas Christos C   Yang Ning N   Rui Hallgeir H   Fuchs Serge Y SY  

Molecular endocrinology (Baltimore, Md.) 20101020 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 depe  ...[more]

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