Meta-Biol

• Pathways

For the ERBB3-binding ERBB2 KD mutants that were shown to activate PI3K/AKT signaling (evidenced by activating phosphorylation of AKT), it is assumed that, like the wild type ERBB2:ERBB3 heterodimer, the heterodimers of these ERBB2 KD mutants with ERBB3 bind to the PI3K complex, leading to conversion of PIP2 to PIP3.

Phosphorylated heterodimers of the following ERBB2 KD mutants with ERBB3 are assumed to, like the wild type ERBB2:ERBB3 heterodimer, recruit and activate the PI3K complex, resulting in conversion of PIP2 to PIP3:

ERBB2 L755S (Kancha et al. 2011, Cocco et al. 2018, Croessmann et al. 2019);
ERBB2 L755P (Kancha et al. 2011);
ERBB2 I767M (Ng et al. 2015);
ERBB2 V777L (Kancha et al. 2011);
ERBB2 T798I (Hanker et al. 2017);
ERBB2 T798M (Kancha et al. 2011, Rexer et al. 2013);
ERBB2 T862A (Kancha et al. 2011);
ERBB2 L869R (Hanker et al. 2017);
ERBB2 H878Y (Kancha et al. 2011, Hu, Hu et al. 2015, Hu, Wan et al. 2015);
ERBB2 Y772_A775dup (Wang et al. 2006)

Activation of PI3K/AKT signaling downstream of the following ERBB2 KD cancer mutants has not been studied and they are annotated as candidates:

ERBB2 L755M
ERBB2 L755W
ERBB2 V777M
ERBB2 V777E
ERBB2 T733I
ERBB2 L869Q
ERBB2 H878R