Meta-Biol

• Pathways

ALK1 is phosphorylated on tyrosine residues in intracellular domain after ligand binding and dimerization, consistent with other receptor tyrosine kinases (Soutto et al, 2001; Stoica et al, 2002; Perez-Pinera et al, 2007; Lee et al, 2010; reviewed in Roskoski, 2013; Della Corte et al, 2018). ALK1, like other members of the insulin receptor subfamily, has a YXXXXYY motif in the activation loop. Trans-phosphorylation of the three tyrosine residues in the activation (Y1278, Y1282 and Y1283) after ligand binding causes a conformational change that relieves autoinhibition of the kinase (Donella-Deana et al, 2005; Tartari et al, 2007; Lee et al, 2010; reviewed in Roskoski et al, 2013). ALK also contains a number of tyrosine residues in the juxtamembrane domain region, at positions 1078, 1092, 1096, 1131, 1358, 1507 and 1604, among others (Rush et al, 2005; Kuo et al, 2007; Degoutin et al, 2007; reviewed in Roskoski, 2013). Whether phosphorylation of these residues precedes activation loop phosphorylation, as is the case for other RTKs, remains to be investigated. In addition, some sites may be phosphorylated by other cellular kinases after ALK auto-phosphorylation (reviewed in Klug et al, 2018; Roskoski, 2013).