Hrs is a positive regulator of VEGF and insulin signaling
Experimental Cell Research, ISSN: 0014-4827, Vol: 313, Issue: 9, Page: 1927-1942
2007
- 13Citations
- 25Captures
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Example: if you select the 1-year option for an article published in 2019 and a metric category shows 90%, that means that the article or review is performing better than 90% of the other articles/reviews published in that journal in 2019. If you select the 3-year option for the same article published in 2019 and the metric category shows 90%, that means that the article or review is performing better than 90% of the other articles/reviews published in that journal in 2019, 2018 and 2017.
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Metrics Details
- Citations13
- Citation Indexes13
- 13
- CrossRef12
- Captures25
- Readers25
- 25
Article Description
Both VEGF and insulin are implicated in the pathogenesis of diabetic retinopathy. While it has been established for many years that the number of cell surface receptors impacts upon VEGF and insulin action, little is known about the precise machinery and proteins driving VEGF-R2 and IR degradation. Here, we investigate the role of Hepatocyte growth factor-Regulated tyrosine kinase Substrate (Hrs), a regulator of RTK trafficking, in VEGF and insulin signaling. We report that ectopic expression of Hrs increases VEGF-R2 and IR number and tyrosine phosphorylation, leading to amplification of their downstream signaling. The UIM (Ubiquitin Interacting Motif) domain of Hrs is required for Hrs-induced increases in VEGF-R2, but not in IR. Furthermore, Hrs is tyrosine-phosphorylated in response to VEGF and insulin. We show that the UIM domain is required for Hrs phosphorylation in response to VEGF, but not to insulin. Importantly, Hrs co-localizes with both VEGF-R2 and IR and co-immunoprecipitates with both in a manner independent of the Hrs-UIM domain. Finally, we demonstrate that Hrs inhibits Nedd4-mediated VEGF-R2 degradation and acts additively with Grb10. We conclude that Hrs is a positive regulator of VEGF-R2 and IR signaling and that ectopic expression of Hrs protects both VEGF-R2 and IR from degradation.
Bibliographic Details
http://www.sciencedirect.com/science/article/pii/S0014482707000857; http://dx.doi.org/10.1016/j.yexcr.2007.02.034; http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=34247507553&origin=inward; http://www.ncbi.nlm.nih.gov/pubmed/17445799; https://linkinghub.elsevier.com/retrieve/pii/S0014482707000857; https://dx.doi.org/10.1016/j.yexcr.2007.02.034
Elsevier BV
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