1. Figure 1 The multidomain structure of c-MET and its ligand, HGF
Figure 1 | The multidomain structure of c-MET and its ligand, HGF. a | The domain structure of c-MET. The extracellular domain comprises a large N-terminal semaphorin (SEMA) domain, which folds into a seven-bladed β-propeller structure, a plexin, semaphorin, and integrin (PSI) domain and four immunoglobulin-like IPT (immunoglobulin- like regions in plexins and transcription factors) domains (IPT1–4), which comprise four disulfide-linked loop structures. The intracellular domain constitutes a juxtamembrane domain (JM), containing Ser975, which negatively regulates c-MET kinase activity upon phosphorylation, and Y1003, which is involved in endocytosis, a tyrosine kinase (TK) domain, containing Y1234 and Y1235, which upregulate kinase activity upon transautophosphorylation and a c-terminal multifunctional docking site (MFDS), which mediates recruitment of cytoplasmic signalling molecules and adaptor proteins via Y1349 and Y1356. b | Domain structure of HGF, comprising the N-terminal (N) hairpin- loop, four kringle domains (K1–K4) of the α-chain, and the c-terminal serine proteinase homology (SPH) domain of the β-chain, which is homologous to serine proteinases, but lacks proteolytic activity.
Bradley, C. A. et al. (2017) Targeting c‑MET in gastrointestinal tumours: rationale, opportunities and challenges
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