Source

Rabbit

Reactivity

Human

Background

Anaplastic lymphoma kinase is a tyrosine kinase receptor for pleiotrophin, a growth factor involved in embryonic brain development. In ALK-expressing cells, PTN induces phosphorylation of both ALK and the downstream effectors IRS-1, Shc, PLCγ, and PI3 kinase. ALK was originally discovered as a nucleophosmin-ALK fusion protein produced by a translocation. Investigators have found that the NPM-ALK fusion protein is a constitutively active, oncogenic tyrosine kinase associated with anaplastic lymphoma. Research literature suggests that activation of PLCγ by NPM-ALK may be a crucial step for its mitogenic activity and involved in the pathogenesis of anaplastic lymphomas.A distinct ALK oncogenic fusion protein involving ALK and echinoderm microtubule-associated protein like 4 has been described in the research literature from a non-small cell lung cancer cell line, with corresponding fusion transcripts present in some cases of lung adenocarcinoma. The short, amino-terminal region of the microtubule-associated protein EML4 is fused to the kinase domain of ALK.Phosphorylated Tyr664 of NPM-ALK is required for the interaction with PLCgamma. Site-directed mutagenesis of this tyrosine residue results in the loss of oncogenic activity of NPM-ALK.

References

[1] Stoica, G.E. et al. (2001) J Biol Chem 276, 16772-9.
[2] Iwahara, T. et al. (1997) Oncogene 14, 439-49.
[3] Morris, S.W. et al. (1997) Oncogene 14, 2175-88.
[4] Morris, S.W. et al. (1994) Science 263, 1281-4.
[5] Bai, R.Y. et al. (1998) Mol Cell Biol 18, 6951-61.
[6] Rikova, K. et al. (2007) Cell 131, 1190-203.
[7] Takeuchi, K. et al. (2008) Clin Cancer Res 14, 6618-24.
[8] Soda, M. et al. (2007) Nature 448, 561-6.

Raw materials

Preparation Products