Meta-Biol

• Pathways

For the following EGFR-binding ERBB2 KD mutants that were shown to activate PI3K/AKT signaling, it is assumed that heterodimers of these mutants with EGFR, like the wild type ERBB2:EGFR heterodimer, bind to the PI3K complex through GRB2:GAB1, leading to 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; heterodimerization with EGFR indirectly shown by Bose et al. 2013);
ERBB2 V777L (Kancha et al. 2011);
ERBB2 G778_P780dup (Suzawa et al. 2016);
ERBB2 T798M (Kancha et al. 2011, Rexer et al. 2013);
ERBB2 T798I (Hanker et al. 2017);
ERBB2 T862A (Kancha et al. 2011);
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 H878R