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Lysosomal EGFR functions as a GEF for Rheb

Tao Hou^1,† , Peiqiang Yan^1,† , Hiroyuki Inuzuka¹ , Wenyi Wei^1,*

¹Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
^†These authors contributed equally: Tao Hou, Peiqiang Yan
* Correspondence: Wenyi Wei(wwei2@bidmc.harvard.edu)

A recent study published in Cell Research revealed that lysosome-localized epidermal growth factor receptor (EGFR) directly binds to and activates Rheb, a key activator of mTORC1, in a kinase activity-independent manner. Mechanistically, EGFR utilizes its Glu804 residue, which likely functions as a catalytic “glutamic finger”, to exert a novel role as a guanine nucleotide exchange factor for Rheb.

https://doi.org/10.1038/s41422-025-01126-3

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