Anti-ALK Antibody Picoband®, PE Conjugate

ALK (Anaplastic lymphoma kinase) also known as ALK tyrosine kinase receptor or CD246 (cluster of differentiation 246) is an enzyme that in humans is encoded by the ALK gene. The ALK gene is mapped on 2p23.2-p23.1. Expressed in the small intestine, testis, and brain but not in normal lymphoid cells, ALK shows greatest sequence similarity to the insulin receptor subfamily of kinases. ALK plays an important role in the development of the brain and exerts its effects on specific neurons in the nervous system. The deduced amino acid sequences reveal that ALK is a novel receptor tyrosine kinase having a putative transmembrane domain and an extracellular domain. In Drosophila, localized Jeb activates Alk and the downstream Ras/mitogen-activated protein kinase cascade to specify a select group of visceral muscle precursors as muscle-patterning pioneers. Functional RNA interference screening on a set of these transcriptional targets revealed that CEBPB and BCL2A1 were absolutely necessary to induce cell transformation and/or to sustain growth and survival of ALK-positive ALCL cells. One particularly informative case presented a high-level gene amplification that was strictly limited to ALK, indicating that this gene may contribute on its own to neuroblastoma development. Mutated ALK proteins were overexpressed, hyperphosphorylated, and showed constitutive kinase activity. The knockdown of ALK expression in ALK-mutated cells, but also in cell lines overexpressing a wildtype ALK, led to a marked decrease of cell proliferation.

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. .

1. Benharroch, D., Meguerian-Bedoyan, Z., Lamant, L., Amin, C., Brugieres, L., Terrier-Lacombe, M.-J., Haralambieva, E., Pulford, K., Pileri, S., Morris, S. W., Mason, D. Y., Delsol, G. ALK-positive lymphoma: a single disease with a broad spectrum of morphology. Blood 91: 2076-2084, 1998. 2. Chen, Y., Takita, J., Choi, Y. L., Kato, M., Ohira, M., Sanada, M., Wang, L., Soda, M., Kikuchi, A., Igarashi, T., Nakagawara, A., Hayashi, Y., Mano, H., Ogawa, S. Oncogenic mutations of ALK kinase in neuroblastoma. Nature 455: 971-974, 2008. 3. Englund, C., Loren, C. E., Grabbe, C., Varshney, G. K., Deleuil, F., Hallberg, B., Palmer, R. H. Jeb signals through the Alk receptor tyrosine kinase to drive visceral muscle fusion. Nature 425: 512-516, 2003.

Store at -20℃ for one year from date of receipt. After reconstitution, at 4℃ for one month. It can also be aliquotted and stored frozen at -20℃ for six months. Avoid repeated freeze-thaw cycles.

Cell membrane ; Single-pass type I membrane protein . Membrane attachment was crucial for promotion of neuron-like differentiation and cell proliferation arrest through specific activation of the MAP kinase pathway.