ALK fusions bind GRB2

Stable Identifier
R-HSA-9710914
Type
Reaction
Species
Homo sapiens
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NPM-ALK, TFG-ALK and ATIC-ALK fusion proteins have been demonstrated to bind GRB2 by GST-pulldown and co-immunoprecipitation (Fujimoto et al, 1996; Trinei et al, 2000; Hernandez et al, 2002). In the case of NPM-ALK, GRB binding is independent of the recruitment of SHC and IRS1, as the GRB2 interaction is not abrogated by the mutation of the primary SHC and IRS binding site at Y567 (Fujimoto et al, 1996). Neither direct binding of GRB2 nor a defined GRB2 binding site have been identified in the context of an ALK fusion protein, and recruitment may be mediated by other adaptor proteins, including PTPN11 (Voena et al, 2007). GRB2 binding appears to contribute to the transformation potential of the ALK fusion proteins, possibly by linking to the MAP kinase signaling pathway (Fujimoto et al, 1996; reviewed in Palmer, 2009). In some ALK fusions, the fusion partner may also be responsible for activation of the MAP kinase signaling pathway, as is the case for EML4-ALK fusions (Hrustanovic et al 2015).

Literature References
PubMed ID Title Journal Year
19459784 Anaplastic lymphoma kinase: signalling in development and disease

Grabbe, C, Vernersson, E, Palmer, RH, Hallberg, B

Biochem. J. 2009
11943732 Diversity of genomic breakpoints in TFG-ALK translocations in anaplastic large cell lymphomas: identification of a new TFG-ALK(XL) chimeric gene with transforming activity

Bellosillo, B, Morris, SW, Pulford, K, Rosenwald, A, Beà, S, Mason, D, Hernández, L, Pinyol, M, Ott, G, Falini, B, Santos, E, Fernández, A, Carbone, A, Campo, E

Am. J. Pathol. 2002
10706082 A new variant anaplastic lymphoma kinase (ALK)-fusion protein (ATIC-ALK) in a case of ALK-positive anaplastic large cell lymphoma

Falini, B, Lanfrancone, L, Campo, E, Trinei, M, Mason, DY, Pelicci, PG, Pulford, K

Cancer Res 2000
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
26301689 RAS-MAPK dependence underlies a rational polytherapy strategy in EML4-ALK-positive lung cancer

Okimoto, RA, Rosell, R, Aisner, DL, Collisson, EA, Doebele, RC, Vaishnavi, A, Riess, JW, Lovly, CM, Blakely, CM, Olivas, V, Ou, SH, Sabnis, A, Bivona, TG, Karachaliou, N, Tulpule, A, Lin, L, Hrustanovic, G, Flanagan, J, Mack, PC, Ichihara, E, Chan, E, Asthana, S, Varella-Garcia, M, Neel, DS, Pazarentzos, E

Nat Med 2015
17483340 The tyrosine phosphatase Shp2 interacts with NPM-ALK and regulates anaplastic lymphoma cell growth and migration

Chiarle, R, Ambrogio, C, Jensen, ON, Inghirami, G, Boccalatte, F, Boeri Erba, E, Mohammed, S, Conte, C, Palestro, G, Voena, C

Cancer Res 2007
Participants
Participates
Disease
Name Identifier Synonyms
cancer DOID:162 malignant tumor, malignant neoplasm, primary cancer
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