ALK mutants bind SHC

Stable Identifier
Reaction [binding]
Homo sapiens
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Early studies with the NPM-ALK fusion identified two putative consensus sequences for phosphotyrosine binding proteins such as SHC. Coimmunoprecipitation studies in NIH 3T3 cells determined that the predominant SHC binding site is at tyrosine 567 (equivalent to Y1507 in the full length protein). SHC is tyrosine phosphorylated and associated with both NPM-ALK and GRB2 in these cells (Fujimoto et al, 1996). SHC has also been demonstrated to be a target of ALK-mediated phosphorylation in ALK-amplified neuroblastoma cells (Miyake et al, 2002). Mutation of the Y567 binding site to F abrogates the binding of SHC to the fusion protein, but does not eliminate the transforming activity of the protein, suggesting that SHC binding is not essential to cellular transformation (Fujimoto et al, 1996). SHC has also been shown to bind to other ALK fusions, including those with TFG, ATIC and FN1 and to contribute to signaling and transformation to various extents (Hernandez et al, 2002; Trinei et al, 2000; Ren et al, 2012; Okubo et al, 2012; Cazes et al, 2013reviewed in Hallberg and Palmer, 2013; Hallberg and Palmer, 2016; Roskoski, 2013)

Literature References
PubMed ID Title Journal Year
27573755 The role of the ALK receptor in cancer biology

Hallberg, B, Palmer, RH

Ann Oncol 2016
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
12185581 Activation of anaplastic lymphoma kinase is responsible for hyperphosphorylation of ShcC in neuroblastoma cell lines

Hakomori, Y, Sakai, R, Miyake, I, Saito, M, Gamou, T, Shinohara, A, Iwamatsu, A

Oncogene 2002
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
22249260 Aberrant activation of ALK kinase by a novel truncated form ALK protein in neuroblastoma

Hayashi, Y, Chen, Y, Igarashi, T, Hiwatari, M, Takita, J, Ogawa, S, Okubo, J, Nishimura, R, Sanada, M, Kato, M, Oki, K

Oncogene 2012
22570254 Identification of anaplastic lymphoma kinase as a potential therapeutic target in ovarian cancer

Haack, H, Ren, JM, Gu, TL, Zhu, X, Innocenti, G, Crosby, K, Tan, ZP, Moritz, A, Yang, YF, Ren, H, Rush, J, Beausoleil, S, Comb, MJ, Zhang, Y, Zhou, XM

Cancer Res 2012
23201355 Anaplastic lymphoma kinase (ALK): structure, oncogenic activation, and pharmacological inhibition

Roskoski, R

Pharmacol. Res. 2013
23139213 Characterization of rearrangements involving the ALK gene reveals a novel truncated form associated with tumor aggressiveness in neuroblastoma

Louis-Brennetot, C, Schleiermacher, G, Loew, D, Pierron, G, Ferrand, S, Daveau, R, Cappo, J, Vigny, M, Jouannet, S, Delattre, O, Dingli, F, Lombard, B, Boeva, V, Cazes, A, Janoueix-Lerosey, I, Combaret, V, Mazot, P, Barillot, E

Cancer Res 2013
24060861 Mechanistic insight into ALK receptor tyrosine kinase in human cancer biology

Palmer, RH, Hallberg, B

Nat. Rev. Cancer 2013
Name Identifier Synonyms
cancer DOID:162 malignant tumor, malignant neoplasm, primary cancer
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