March 2012
Volume 53, Issue 14
ARVO Annual Meeting Abstract  |   March 2012
IGF-1R/INSR Hybrid in Proliferating Corneal Epithelial Cells
Author Affiliations & Notes
  • Yu-Chieh Wu
    Ophthalmology, Univ of Texas Southwestern Med Ctr, Dallas, Texas
  • Meifang Zhu
    Ophthalmology, Univ of Texas Southwestern Med Ctr, Dallas, Texas
  • Danielle M. Robertson
    Ophthalmology, Univ of Texas Southwestern Med Ctr, Dallas, Texas
  • Footnotes
    Commercial Relationships  Yu-Chieh Wu, None; Meifang Zhu, None; Danielle M. Robertson, None
  • Footnotes
    Support  NIH Grant R01 EY018219 (DMR), Core Grant EY020799, OneSight Research Foundation, Dallas, Texas (DMR), and a Career Development Award (DMR) and an unrestricted grant from Research to Prevent Blindness
Investigative Ophthalmology & Visual Science March 2012, Vol.53, 1826. doi:
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      Yu-Chieh Wu, Meifang Zhu, Danielle M. Robertson; IGF-1R/INSR Hybrid in Proliferating Corneal Epithelial Cells. Invest. Ophthalmol. Vis. Sci. 2012;53(14):1826.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose: : Type I insulin-like growth factor receptor (IGF-1R) and insulin receptor (INSR) are highly homologous molecules, which heterodimerize to form IGF-1R/INSR hybrid (Hybrid-R). The nuclear localization of IGF-1R was recently shown in human corneal epithelial cells; however, the function of nuclear IGF-1R is not generally clear and the presence of the Hybrid-R is unknown. The purpose of this study is to characterize the role of IGF-1/IGF-1R and Hybrid-R signaling and the presence and biological significance of Hybrid-R in cultured human corneal epithelial cells.

Methods: : IGF-1-mediated cell growth and signaling were examined in a human telomerized corneal epithelial (hTCEpi) cell line using reducing immunoprecipitation, immunoblotting and cell proliferation assays. The presence of Hybrid-R in hTCEpi and primary cultured human corneal epithelial cells was confirmed by immunofluorescence and reciprocal immunoprecipitation of whole cell lysates. The nuclear profile of IGF-1R/IGF-1R homodimer and Hybrid-R was determined in nuclear extracts of hTCEpi cells using immunoprecipitation with anti-IGF-1R (αIR3) and anti-INSR, followed by immunoblots with anti-IGF-1R. Chromatin-immunoprecipitation (ChIP)-sequencing with anti-IGF-1R and anti-INSR was used to identify potential genomic targets in hTCEpi cells.

Results: : In cultured hTCEpi cells, IGF-1 stimulated Akt signaling and promoted cell growth through IGF-1R activation; insulin at the same concentration did not show a significant effect. Reciprocal immunoprecipitation with antibodies against either anti-IGF-1R or anti-INSR verified the presence of Hybrid-R in human corneal epithelium; Hybrid-R was only activated by IGF-1. Double-labeling experiments demonstrated co-localization of IGF-1R with INSR in the nucleus. Importantly, the presence of Hybrid-R, but not IGF-1R/IGF-1R homodimer, was detected in nuclear extracts of hTCEpi cells. DNA sequencing following ChIP identified novel gene targets involved in corneal epithelial cell proliferation and survival pathways.

Conclusions: : In addition to mediating events at the plasma membrane, IGF-1R/INSR hybrid localizes to the nucleus in proliferating corneal epithelial cells and binds to genomic targets involved in proliferation. Taken together, these data suggest a role for Hybrid-R in mediating proliferative events in the corneal epithelium.

Keywords: cornea: epithelium • growth factors/growth factor receptors • proliferation 

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