Mutual regulation between IGF‐1R and IGFBP‐3 in human corneal epithelial cells. Issue 2 (5th August 2018)

• Record Type: Journal Article
• Authors: Titone, Rossella; Zhu, Meifang; Robertson, Danielle M.
• Is Part Of: Journal of cellular physiology. Volume 234:Issue 2(2019:Feb.)
• Page Start: 1426
• Page End: 1441
• Publication Date: 2018-08-05
• Subjects: cornea -- epithelium -- insulin‐like growth factor type 1 receptor (IGF‐1R) -- insulin‐like growth factor binding protein‐3 (IGFBP‐3) -- insulin -- SUMO; Physiology -- Periodicals; Cell physiology -- Periodicals; 571.6
• DOI: 10.1002/jcp.26948
• Languages: English
• ISSNs: 0021-9541

Abstract

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. Abstract : Here we report that the insulin‐like growth factor binding protein‐3 (IGFBP‐3) mediates nuclear translocation of insulin‐like growth factor type 1 receptor (IGF‐1R) in response to stress. This occurs via SUMOylation by SUMO 2/3. This is the first study to show a direct relationship between IGF‐1R and IGFBP‐3 in the maintenance of corneal epithelial homeostasis.