ERBB4 and neoplasm: It is not surprising that targeting the canonical site of ErbB4 binding (at ErbB4 phospho-Tyr1056) to the regulatory subunit of the PI3 kinase (through either the Y1056F or K751M mutations) disrupts the tumor suppressor activity of the constitutively-active ErbB4 Q646C mutant; the Y1056F or K751M mutations are predicted to prevent ErbB4 from coupling to PI3 kinase activity and to its pro-proliferative, anti-apoptotic effectors.