ERBB4 and neoplasm: HER3-mediated signaling involves the MAPK/ERK, PI3K/AKT/MTOR, JAK/STAT, and PKC protein kinase pathways.[16] In general, HER3-containing heterodimers (i.e. HER2/HER3 and HER3/HER4) are tumor-promoting.[17] On the other hand, HER4-mediated signaling results in either pro-tumor or anti-tumor effects through multiple protein kinase pathways, including JAK/STAT and PI3K/AKT.