ErbB3/HER3

ErbB3/HER3 is an EGFR/ErbB family receptor activated by neuregulin-1 and neuregulin-2, but it lacks intrinsic kinase activity and signals through heterodimers with EGFR, ErbB2/HER2, or ErbB4/HER4^[1]. Mechanistically, HER3 contains six PI3K p85 docking sites, making it a signaling specialist for PI3K/AKT regulation of metabolism, proliferation, survival, and angiogenesis^[1]. In cancer models, HER3 signaling contributes to breast cancer progression, HER2-amplified tumor aggressiveness, and resistance to EGFR- or HER2-targeted therapies^[1][2][3]. Compared with kinase-active EGFR, HER2, and HER4, HER3 functions mainly as a kinase-impaired co-receptor that amplifies partner-driven signaling rather than acting as an autonomous kinase target^[2][4]. In defined Ba/F3 models, ERBB3 co-expression enhanced NRG1-stimulated ERBB3/ERBB4 phosphoproteome regulation and proliferation, supporting its use in pathway-dissection experiments^[5]. For experimental applications, HER3-directed antibodies can block PI3K/AKT signaling, induce receptor ubiquitination and degradation, and support mechanistic studies of HER3-dependent tumor signaling^[6].