Ligand-stimulated ERBB4 was shown to form heterodimers with ligand-stimulated EGFR when human ERBB4 and EGFR were exogenously expressed in mouse fibroblast cell line. Heterodimers of ERBB4 and EGFR undergo trans-autophosphorylation, but the exact phosphorylation pattern, downstream signaling and physiological significance of these heterodimers have not been studied (Riese et al. 1995, Cohen et al. 1996). Binding of ERBB4 CYT2 isoform to EGFR protects EGFR from ligand-induced degradation by preventing binding of the CBL:GRB2 complex to EGFR (Kiuchi et al. 2014).
Andrews, GC, Riese DJ, 2nd, Stern, DF, Plowman, GD, van Raaij, TM
Fell, HP, Foy, L, Green, JM, Cohen, BD
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