|Other Names||ALK tyrosine kinase receptor, Anaplastic lymphoma kinase, CD246, ALK|
|Format||Synthetic peptide was lyophilized with 100% acetonitrile and is supplied as a powder. Reconstitute with 0.1 ml DI water for a final concentration of 1 mg/ml.|
|Storage||Maintain refrigerated at 2-8°C for up to 6 months. For long term storage store at -20°C.|
|Precautions||This product is for research use only. Not for use in diagnostic or therapeutic procedures.|
|Function||Neuronal orphan receptor tyrosine kinase that is essentially and transiently expressed in specific regions of the central and peripheral nervous systems and plays an important role in the genesis and differentiation of the nervous system. Transduces signals from ligands at the cell surface, through specific activation of the mitogen-activated protein kinase (MAPK) pathway. Phosphorylates almost exclusively at the first tyrosine of the Y-x-x-x-Y-Y motif. Following activation by ligand, ALK induces tyrosine phosphorylation of CBL, FRS2, IRS1 and SHC1, as well as of the MAP kinases MAPK1/ERK2 and MAPK3/ERK1. Acts as a receptor for ligands pleiotrophin (PTN), a secreted growth factor, and midkine (MDK), a PTN-related factor, thus participating in PTN and MDK signal transduction. PTN-binding induces MAPK pathway activation, which is important for the anti-apoptotic signaling of PTN and regulation of cell proliferation. MDK-binding induces phosphorylation of the ALK target insulin receptor substrate (IRS1), activates mitogen-activated protein kinases (MAPKs) and PI3-kinase, resulting also in cell proliferation induction. Drives NF-kappa-B activation, probably through IRS1 and the activation of the AKT serine/threonine kinase. Recruitment of IRS1 to activated ALK and the activation of NF-kappa-B are essential for the autocrine growth and survival signaling of MDK.|
|Cellular Location||Cell membrane; Single-pass type I membrane protein Note=Membrane attachment was crucial for promotion of neuron-like differentiation and cell proliferation arrest through specific activation of the MAP kinase pathway|
|Tissue Location||Expressed in brain and CNS. Also expressed in the small intestine and testis, but not in normal lymphoid cells|
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The 2;5 chromosomal translocation is frequently associatedwith anaplastic large cell lymphomas (ALCLs). The translocationcreates a fusion gene consisting of the ALK (anaplastic lymphomakinase) gene and the nucleophosmin (NPM) gene: the 3' half of ALK,derived from chromosome 2, is fused to the 5' portion of NPM fromchromosome 5. A recent study shows that the product of the NPM-ALKfusion gene is oncogenic. The deduced amino acid sequences revealthat ALK is a novel receptor protein-tyrosine kinase having aputative transmembrane domain and an extracellular domain. Thesesequences are absent in the product of the transforming NPM-ALKgene. ALK shows the greatest sequence similarity to LTK (leukocytetyrosine kinase). ALK plays an important role in the development ofthe brain and exerts its effects on specific neurons in the nervoussystem.
Ardini, E., et al. Cancer Lett. 299(2):81-94(2010)Ohira, M., et al. Cancer Sci. 101(11):2295-2301(2010)Merkel, O., et al. Proc. Natl. Acad. Sci. U.S.A. 107(37):16228-16233(2010)De Brouwer, S., et al. Clin. Cancer Res. 16(17):4353-4362(2010)Bossi, R.T., et al. Biochemistry 49(32):6813-6825(2010)
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