ERBB4 forms heterodimers with EGFR

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).

研究表明，当在鼠成纤维细胞系中异源表达人源ERBB4和EGFR时，配体激活的ERBB4可形成与配体激活的EGFR的异源二聚体。ERBB4和EGFR的异源二聚体经历跨自磷酸化，但其确切的磷酸化模式、下游信号传导及其生理学意义尚未得到研究（Riese等人，1995年，Cohen等人，1996年）。ERBB4 Cyt2亚型与EGFR的结合通过阻止CBL:GRB2复合物与EGFR的结合，从而保护EGFR免受配体诱导的降解（Kiuchi等人，2014年）。