Reactome | Active ALK phosphorylates IRS1

Active ALK phosphorylates IRS1

Stable Identifier

R-HSA-9700168

Type

Reaction [transition]

Species

Homo sapiens

Compartment

plasma membrane, cytosol

ReviewStatus

5/5

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IRS1 is phosphorylated downstream of active ALK 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 IRS1 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 Turner and Alexander, 2006; 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
16482213	Fusion tyrosine kinase mediated signalling pathways in the transformation of haematopoietic cells Turner, SD, Alexander, DR	Leukemia	2006
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