ERBB receptor feedback inhibitor 1 (MIG6)

ERBB receptor feedback inhibitor 1 (MIG6) is a cytoplasmic regulatory protein encoded by the *ERRFI1* gene that functions as a negative feedback inhibitor of the epidermal growth factor receptor (EGFR) and other ERBB family members. MIG6 directly binds activated EGFR, inhibiting its kinase activity and promoting receptor internalization and degradation. This process is tightly regulated, involving phosphorylation of MIG6 by EGFR and Src kinases. Functional loss or decreased expression of MIG6 removes this regulatory brake on EGFR, promoting abnormal cell growth and contributing to cancer progression, notably in glioblastoma and other malignancies. The balance of EGFR and MIG6 levels is critical for normal cellular responses and is a growing focus for biomarker-driven cancer therapies.

Other names

Mitogen-inducible gene 6 (MIG6)ERRFI1gene-33 (in rats)

Loss or mutation of MIG6/ERRFI1 leads to aberrant activation of EGFR, enhances cellular transformation and oncogenic growth, and may serve as a resistance factor to EGFR inhibitors. Normal function: Direct inhibition of EGFR kinase activity, competitive inhibition for substrate/ligand binding, and promotion of receptor downregulation.