Active ALK phosphorylates IRS1

Stable Identifier
R-HSA-9700168
Type
Reaction
Species
Homo sapiens
Compartment
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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).

Literature References
PubMed ID Title Journal Year
15226403 ALK receptor tyrosine kinase promotes cell growth and neurite outgrowth

Kotani, M, Motegi, A, Sakuraba, H, Fujimoto, J, Yamamoto, T

J. Cell. Sci. 2004
29455642 Role and targeting of anaplastic lymphoma kinase in cancer

Troiani, T, Viscardi, G, Morgillo, F, Fasano, M, Martinelli, E, Ciardiello, F, Della Corte, CM, Di Liello, R

Mol. Cancer 2018
18097461 The anaplastic lymphoma kinase in the pathogenesis of cancer

Chiarle, R, Piva, R, Ambrogio, C, Inghirami, G, Voena, C

Nat. Rev. Cancer 2008
8633037 Characterization of the transforming activity of p80, a hyperphosphorylated protein in a Ki-1 lymphoma cell line with chromosomal translocation t(2;5)

Yamamoto, T, Iwahara, T, Satoh, H, Seki, N, Fujimoto, J, Mori, S, Shiota, M

Proc. Natl. Acad. Sci. U.S.A. 1996
23201355 Anaplastic lymphoma kinase (ALK): structure, oncogenic activation, and pharmacological inhibition

Roskoski, R

Pharmacol. Res. 2013
11278720 Identification of anaplastic lymphoma kinase as a receptor for the growth factor pleiotrophin

Wellstein, A, Caughey, DJ, Kuo, AH, Karavanov, A, Sunitha, I, Malerczyk, C, Aigner, A, Riegel, AT, Souttou, B, Stoica, GE, Wen, D

J Biol Chem 2001
Participants
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Catalyst Activity

protein tyrosine kinase activity of Active ALK:IRS1 [plasma membrane]

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