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).
Kotani, M, Motegi, A, Sakuraba, H, Fujimoto, J, Yamamoto, T
Troiani, T, Viscardi, G, Morgillo, F, Fasano, M, Martinelli, E, Ciardiello, F, Della Corte, CM, Di Liello, R
Chiarle, R, Piva, R, Ambrogio, C, Inghirami, G, Voena, C
Yamamoto, T, Iwahara, T, Satoh, H, Seki, N, Fujimoto, J, Mori, S, Shiota, M
Roskoski, R
Wellstein, A, Caughey, DJ, Kuo, AH, Karavanov, A, Sunitha, I, Malerczyk, C, Aigner, A, Riegel, AT, Souttou, B, Stoica, GE, Wen, D
protein tyrosine kinase activity of Active ALK:IRS1 [plasma membrane]
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