Clinical Significance of HER-2 Splice Variants in Breast Cancer Progression and Drug Resistance
Figure 2
Schematic of HER-2 structure, activation, and signalling. (a) HER-2 is a single transmembrane cell surface receptor with extracellular, transmembrane, and intracellular regions. The extracellular region comprises of two ligand-binding domains (L I and L II) and two cysteine-rich domains (C I and C II) [8]. Intracellularly, HER-2 receptors have intrinsic tyrosine kinase activity (TK). (b) HER-2 does not bind ligands but is activated by forming heterodimers with other ErbB receptors via interaction at the cysteine-rich domains. This results in autophosphorylation of the tyrosine kinase domains and induction of downstream signalling. Normal signalling includes stimulation of the PI3K/AKT pathway which induces survival mechanisms and inhibits apoptosis, whilst the RAS/RAF/MEK/MAPK pathway stimulates cell proliferation [8].
