Meta-Biol

• Pathways

IRS1 is phosphorylated downstream of active ALK1 in a manner that is dependent on ALK kinase activity. Based on studies in NPM-ALK fusions, ALK likely phosphorylates IRS1 on one or more tyrosine residues, but the target amino acid(s) have not been identified directly in the context of the full-length ALK receptor (Fujimoto et al 1996; Stoica et al, 2001; Motegi et al, 2004; reviewed in Roskoski, 2013; Delle Corte et al, 2018). ALK-dependent IRS phosphorylation activates the MAP kinase signaling pathway and promotes cellular proliferation, but direct binding of a RAS GEF such as GRB2:SOS1 has not been shown (reviewed in Chiarle et al, 2008; Roskoski, 2013).