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	Figure 1. Domain structure of human ALK and human LTKThe N-terminal region of human ALK (hALK) comprises two MAM domains (amino acids 264–427 and 480–626), one LDLa domain (amino acids 453–471) and a glycine rich (G-rich) region (amino acids 816–940). A transmembrane (TM)-spanning segment, connects the extracellular region with the protein tyrosine kinase (PTK), domain (amino acids 1116–1383)-containing intracellular region. The closest family member, LTK [hLTK (human LTK)], is depicted with the corresponding regions denoted. The signal peptide (amino acids 1–16), the glycine rich, G-rich, domain (amino acids 63–334) and the kinase domain (amino acids 510–777) located in the intracellular C-terminal region of the protein.
	Figure 2. Signalling via ALKSignalling via dALK occurs via binding of the ligand Jeb, downstream activation of ERK and transcription of downstream target genes. Signalling via mammalian ALK is thought to occur via ligand-mediated dimerization in response to the MK and PTN ligands. ALK mediates signalling via the JAK/STAT, RAS/MAPK, PI3K and PLCγ pathways. Activation of ALK via RPTPβ/ζ, independently of direct ALK–ligand interactions has also been proposed. Lastly, ALK is proposed to function as a dependency receptor which is cleaved by caspase 3 (Casp. 3) in the absence of ligand, thereby promoting apoptosis.
	Figure 3. Tyrosine residues phosphorylated in the intracellular regions of human and mouse ALKThe intracellular regions of human and mouse ALK (hALK and mALK respectively) contain the PTK domain. Potential autophosphorylation sites are shown within human and mouse ALK [11]. Note that there is no equivalent tyrosine residue in mouse ALK for human Tyr1604. Tyrosine residues within the activation loop are shown in bold. In italics is a profiling of putative phosphorylated tyrosine residues in NPM–ALK from ALCL cancer cells [166]. Four tyrosine sites, marked with*, have been tested by mutagenesis in NPM–ALK for interaction with signalling proteins such as PLC-γ (Tyr1604 in hALK) [11], Shc (Tyr1507 in hALK) [115], Src (Tyr1358 in hALK) [157], IRS-1 (Tyr1096 in hALK) [115] and SNT (Tyr1096 and Tyr1507 in hALK) [37]. Localization of tyrosine residues within the intracellular region is not to scale. TM, transmembrane domain.

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