ALK fusions bind FRS

Stable Identifier
Reaction [binding]
Homo sapiens
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NPM-ALK binds to FRS2 and FRS3 as assessed by co-immunoprecipitation from HEK293 cells. FRS proteins bind through three distinct sites, two of which (Y156 and Y567) are dependent on ALK tyrosine phosphorylation, while the third site encompassing residues 631-649 is phosphorylation independent. All three sites contribute to NPM-ALK-mediated transformation (Chikamori et al, 2007; Koshiba et al, 2010). FRS adaptor proteins may contribute to transformation by activating the MAP kinase or PI3K pathways but this has not been directly demonstrated in the case of ALK or ALK fusion signaling (reviewed in Palmer et al, 2009; Gotoh, 2008, Sato and Gotoh, 2009).

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
17086210 Identification of multiple SNT-binding sites on NPM-ALK oncoprotein and their involvement in cell transformation

Yamamoto, T, Tokai-Nishizumi, N, Fujimoto, J, Chikamori, M

Oncogene 2007
19456272 The FRS2 family of docking/scaffolding adaptor proteins as therapeutic targets of cancer treatment

Sato, T, Gotoh, N

Expert Opin Ther Targets 2009
20454865 Structural basis for the recognition of nucleophosmin-anaplastic lymphoma kinase oncoprotein by the phosphotyrosine binding domain of Suc1-associated neurotrophic factor-induced tyrosine-phosphorylated target-2

Tochio, N, Kasai, T, Shirouzu, M, Watanabe, S, Kigawa, T, Yamamoto, T, Yabuki, T, Motoda, Y, Tomizawa, T, Harada, T, Tanaka, A, Koshiba, S, Yokoyama, S, Li, H

J Struct Funct Genomics 2010
18452557 Regulation of growth factor signaling by FRS2 family docking/scaffold adaptor proteins

Gotoh, N

Cancer Sci 2008
Name Identifier Synonyms
cancer DOID:162 malignant tumor, malignant neoplasm, primary cancer
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