University of Maryland School of Medicine, Department of Pathology, University of Maryland Greenebaum Cancer Center, USA
Signaling and cellular activity
In contrast to other ErbB proteins, ErbB3 is not transforming when overexpressed or constitutively activated (Alimandi et al., 1995). Once phosphorylated by other ErbB family members or Src, Met or BRK, ErbB-3 can then bind numerous other signaling proteins. Activation of the PI-3 kinase-AKT pathway is especially important as there are six docking sites for the p85 subunit of PI-3K in the ErbB3 cytoplasmic tail at Tyr 1035, 1178, 1203/1205, 1257 and 1270. AKT regulates many downstream signaling nodes, in particular the two mTOR containing complexes. ErbB3 can also activate the MAPK pathway via its interactions with Grb7 (Tyr 1180,1243) and SHC (1309) (Hynes and Lane, 2005). Thus, ErbB3 is important in biological processes such as translation, apoptosis, nutrient sensing, metabolic regulation, angiogenesis and cell cycle control. Increased expression or activity of ErbB3 has been associated with resistance to EGFR and ErbB2 inhibitors (Sergina et al., 2007) and hormonal therapies (Liu et al., 2007). ErbB3 when localized in the nucleus acts as a transcription factor to regulate Cyclin D1 and β-casein genes (Andrique et al., 2012).
ErbB3 knock-out mice die by E13.5 with defective heart valve formation, but normal heart trabeculation. The animals show a generalized neural crest defects and lack Schwann cell precursors (Erickson et al., 1997). Due to the importance of ErbB3 in breast cancer, the role of ErbB3 in mammary development has been well-studied. ErbB3 is required for ductal morphogenesis in the mouse mammary gland (Stern, 2003). ErbB3 has also been implicated in maintenance of the luminal epithelial subtype in the breast (Balko et al., 2012).
Smita Awasthi ; Anne W Hamburger
ERBB3 (v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (avian))
Atlas Genet Cytogenet Oncol Haematol. 2012-05-01
Online version: http://atlasgeneticsoncology.org/gene/40479/erbb3id40479ch12q13