Mutual regulation between IGF-1R and IGFBP-3 in human corneal epithelial cells

Rossella Titone, Meifang Zhu, Danielle M. Robertson

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

The insulin-like growth factor type 1 receptor (IGF-1R) is part of the receptor tyrosine kinase superfamily. The activation of IGF-1R regulates several key signaling pathways responsible for maintaining cellular homeostasis, including survival, growth, and proliferation. In addition to mediating signal transduction at the plasma membrane, in serum-based models, IGF-1R undergoes SUMOylation by SUMO 1 and translocates to the nucleus in response to IGF-1. In corneal epithelial cells grown in serum-free culture, however, IGF-1R has been shown to accumulate in the nucleus independent of IGF-1. In this study, we report that the insulin-like growth factor binding protein-3 (IGFBP-3) mediates nuclear translocation of IGF-1R in response to growth factor withdrawal. This occurs via SUMOylation by SUMO 2/3. Further, IGF-1R and IGFBP-3 undergo reciprocal regulation independent of PI3k/Akt signaling. Thus, under healthy growth conditions, IGFBP-3 functions as a gatekeeper to arrest the cell cycle in G0/G1, but does not alter mitochondrial respiration in cultured cells. When stressed, IGFBP-3 functions as a caretaker to maintain levels of IGF-1R in the nucleus. These results demonstrate mutual regulation between IGF-1R and IGFBP-3 to maintain cell survival under stress. This is the first study to show a direct relationship between IGF-1R and IGFBP-3 in the maintenance of corneal epithelial homeostasis.

Original languageEnglish (US)
JournalJournal of Cellular Physiology
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

IGF Type 1 Receptor
Insulin-Like Growth Factor Binding Protein 3
Epithelial Cells
Sumoylation
Cells
Insulin-Like Growth Factor I
Homeostasis
human IGFBP3 protein
Signal transduction
Cell membranes
Growth
Cell Cycle Checkpoints
Serum
Cultured Cells
Signal Transduction
Cell Survival
Intercellular Signaling Peptides and Proteins
Respiration
Chemical activation
Maintenance

Keywords

  • cornea
  • epithelium
  • insulin
  • insulin-like growth factor binding protein-3 (IGFBP-3)
  • insulin-like growth factor type 1 receptor (IGF-1R)
  • SUMO

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

Cite this

Mutual regulation between IGF-1R and IGFBP-3 in human corneal epithelial cells. / Titone, Rossella; Zhu, Meifang; Robertson, Danielle M.

In: Journal of Cellular Physiology, 01.01.2018.

Research output: Contribution to journalArticle

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