Regulator of epidermal growth factor signaling: Sprouty

Sprouty was first discovered through its downregulatory effect on fibroblast growth factor (FGF) receptor pathway during tracheal development. Sprouty expression is also induced by the epidermal growth factor receptor (EGFR) cascade in some tissues, including the follicle cells of the ovary, the wing, and eye imaginal disc, and acts to abolish mitogen-activated protein (MAP) kinase activated by EGFR signaling. Sprouty is an intracellular protein that translocates to membrane ruffles upon EGF stimulation by virtue of a translocatory domain within its highly conserved cysteine-rich C-terminal region. Human Sprouty2 (hSpry2) binds the catalytic RING Finger of Casitas B-lineage lymphoma (c-Cbl), an E3 ubiquitin ligase that has been identified to target EGFR degradation. Overexpressed hSpry2 induces a prolonged EGFR-mediated MAP kinase activation. hSpry2 acts to sequester c-Cbl molecules from activated EGFR and impedes EGFR ubiquitination and downregulation, thereby potentiating the amplitude and longevity of intracellular signals. The strategies described herein encompass various methods that have been used to measure the status of EGFR following ectopic expression of hSpry2.