Document Type
Article
Publication Date
12-5-2016
Abstract
Although the growth factor progranulin was discovered more than two decades ago, the functional receptor remains elusive. Here, we discovered that EphA2, a member of the large family of Ephrin receptor tyrosine kinases, is a functional signaling receptor for progranulin. Recombinant progranulin bound with high affinity to EphA2 in both solid phase and solution. Interaction of progranulin with EphA2 caused prolonged activation of the receptor, downstream stimulation of mitogen-activated protein kinase and Akt, and promotion of capillary morphogenesis. Furthermore, we found an autoregulatory mechanism of progranulin whereby a feed-forward loop occurred in an EphA2-dependent manner that was independent of the endocytic receptor sortilin. The discovery of a functional signaling receptor for progranulin offers a new avenue for understanding the underlying mode of action of progranulin in cancer progression, tumor angiogenesis, and perhaps neurodegenerative diseases.
Recommended Citation
Neill, Thomas; Buraschi, Simone; Goyal, Atul; Sharpe, Catherine; Natkanski, Elizabeth; Schaefer, Liliana; Morrione, Andrea; and Iozzo, Renato V., "EphA2 is a functional receptor for the growth factor progranulin." (2016). Department of Pathology, Anatomy, and Cell Biology Faculty Papers. Paper 217.
https://jdc.jefferson.edu/pacbfp/217
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-Share Alike 3.0 License.
PubMed ID
27903606
Comments
This article has been peer reviewed. It is the author’s final published version in Journal of Cell Biology
Volume 215, Issue 5, December 2016, Pages 687-703.
The published version is available at DOI: 10.1083/jcb.201603079. Copyright © Neill et al.