Insulin receptor plasma membrane levels increased by the progesterone receptor membrane component 1

Kaia K. Hampton, Katie Anderson, Hilaree Frazier, Olivier Thibault, Rolf J. Craven

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

The insulin receptor (IR) is a ligand-activated receptor tyrosine kinase that has a key role in metabolism, cellular survival, and proliferation. Progesterone receptor membrane component 1 (PGRMC1) promotes cellular signaling via receptor trafficking and is essential for some elements of tumor growth and metastasis. In the present study, we demonstrate that PGRMC1 coprecipitates with IR. Furthermore, we show that PGRMC1 increases plasma membrane IR levels in multiple cell lines and decreases insulin binding at the cell surface. The findings have therapeutic applications because a small-molecule PGRMC1 ligand, AG205, also decreases plasma membrane IR levels. However, PGRMC1 knockdown via short hairpin RNA expression and AG205 treatment potentiated insulin-mediated phosphorylation of the IR signaling mediator AKT. Finally, PGRMC1 also increased plasma membrane levels of two key glucose transporters, GLUT-4 and GLUT-1. Our data support a role for PGRMC1 maintaining plasma membrane pools of the receptor, modulating IR signaling and function.

Original languageEnglish
Pages (from-to)665-673
Number of pages9
JournalMolecular Pharmacology
Volume94
Issue number1
DOIs
StatePublished - 2018

Bibliographical note

Funding Information:
This work was supported by Washington University Diabetes Research Center Grant P30 DK020579-40; University of Kentucky CTSA Grant UL1 TR001998; and National Institutes of Health National Institute on Aging [Grant 5R01AG033649-08] and National Institutes of Health [Grant T32 DK007778 (to K.K.H. and H.F.)]. https://doi.org/10.1124/mol.117.110510. s This article has supplemental material available at molpharm. aspetjournals.org.

Publisher Copyright:
© 2018 by The American Society for Pharmacology and Experimental Therapeutics.

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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