Figure 1.

The ALK receptor kinase: its domains, pathways, mutations and inhibitors. The different domains of ALK are shown within their bordering amino-acid positions. The major mutations found by Mossé et al.⁴, Janoueix-Lerosey et al.⁵, Chen et al.⁶ and George et al.⁷ in the kinase domain and their relative frequencies (somatic or germline) are shown. The percentage of tumors that show ALK amplification or contain ALK mutations is indicated. Representative small-molecule kinase inhibitors that also inhibit ALK are listed according to their current status. The ALK breakpoint that leads to fusion proteins in different cancers is indicated. SigP, signal peptide; LBD, ligand binding domain; PTN, pleiotrophin; TM, transmembrane domain; IRS-1, insulin receptor substrate 1; Grb2, growth factor receptor–bound protein-2; mTOR, mammalian target of rapamycin.