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Rabbit Anti-ALK (Phosphorylated Y1507) Recombinant Antibody (D6F1V) (PTM-CBMAB-0635LY)


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Published Data
Rabbit Anti-ALK (Phosphorylated Y1507) Recombinant Antibody (D6F1V) in WB
Western blot showing the total NPM-ALK, phospho-NPM-ALK in Karpas-299 cells following 24 h treatment with crizotinib (500 nM). ...View More
Sorrentino, D., Frentzel, J., Mitou, G., Blasco, R. B., Torossian, A., Hoareau-Aveilla, C., ... & Giuriato, S. (2020). High levels of mir-7-5p potentiate crizotinib-induced cytokilling and autophagic flux by targeting raf1 in npm-alk positive lymphoma cells. Cancers, 12(10), 2951.
Rabbit Anti-ALK (Phosphorylated Y1507) Recombinant Antibody (D6F1V) in WB
The expression of cell cycle protein was obviously changed over time. ...View More
Chen, K., Lv, F., Xu, G., Zhang, M., Wu, Y., & Wu, Z. (2016). Phosphoproteomics reveals ALK promote cell progress via RAS/JNK pathway in neuroblastoma. Oncotarget, 7(46), 75968.

Summary

Host Animal
Rabbit
Specificity
Human
Clone
D6F1V
Antibody Isotype
IgG
Application
WB, IP, IF, FC

Basic Information

Immunogen
Synthetic phosphopeptide corresponding to residues surrounding Tyr1507 of human ALK protein.
Host Species
Rabbit
Specificity
Human
Antibody Isotype
IgG
Clonality
Monoclonal
Application Notes
The COA includes recommended starting dilutions, optimal dilutions should be determined by the end user.
ApplicationNote
WB1:1,000
IP1:100
IF(ICC)1:400
FC1:200

Formulations & Storage [For reference only, actual COA shall prevail!]

Format
Liquid
Buffer
HEPES, pH 7.5, 150 mM NaCl, 100 µg/ml BSA, 50% glycerol
Preservative
0.02% sodium azide
Concentration
Batch dependent
Storage
Store at +4°C short term (1-2 weeks). Aliquot and store at -20°C long term. Avoid repeated freezethaw cycles.

Target

Full Name
ALK Receptor Tyrosine Kinase
Introduction
This gene encodes a receptor tyrosine kinase, which belongs to the insulin receptor superfamily. This protein comprises an extracellular domain, an hydrophobic stretch corresponding to a single pass transmembrane region, and an intracellular kinase domain. It plays an important role in the development of the brain and exerts its effects on specific neurons in the nervous system. This gene has been found to be rearranged, mutated, or amplified in a series of tumours including anaplastic large cell lymphomas, neuroblastoma, and non-small cell lung cancer. The chromosomal rearrangements are the most common genetic alterations in this gene, which result in creation of multiple fusion genes in tumourigenesis, including ALK (chromosome 2)/EML4 (chromosome 2), ALK/RANBP2 (chromosome 2), ALK/ATIC (chromosome 2), ALK/TFG (chromosome 3), ALK/NPM1 (chromosome 5), ALK/SQSTM1 (chromosome 5), ALK/KIF5B (chromosome 10), ALK/CLTC (chromosome 17), ALK/TPM4 (chromosome 19), and ALK/MSN (chromosome X).[provided by RefSeq, Jan 2011]
Entrez Gene ID
Human238
Mouse11682
Rat266802
UniProt ID
HumanQ9UM73
MouseP97793
RatF1LRZ0
Function
Neuronal 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. Thinness gene involved in the resistance to weight gain: in hypothalamic neurons, controls energy expenditure acting as a negative regulator of white adipose tissue lipolysis and sympathetic tone to fine-tune energy homeostasis (By similarity).
Biological Process
Activation of MAPK activity Source: UniProtKB
Adult behavior Source: Ensembl
Energy homeostasis Source: UniProtKB
Hippocampus development Source: Ensembl
Multicellular organism development Source: GO_Central
Negative regulation of lipid catabolic process Source: UniProtKB
Neuron development Source: UniProtKB
Phosphorylation Source: UniProtKB
Positive regulation of dendrite development Source: UniProtKB
Positive regulation of kinase activity Source: GO_Central
Positive regulation of NF-kappaB transcription factor activity Source: UniProtKB
Protein autophosphorylation Source: UniProtKB
Regulation of apoptotic process Source: UniProtKB
Regulation of cell population proliferation Source: GO_Central
Regulation of dopamine receptor signaling pathway Source: Ensembl
Regulation of neuron differentiation Source: GO_Central
Response to environmental enrichment Source: Ensembl
Signal transduction Source: UniProtKB
Swimming behavior Source: Ensembl
Transmembrane receptor protein tyrosine kinase signaling pathway Source: GO_Central
Cellular Location
Cell membrane. Membrane attachment was crucial for promotion of neuron-like differentiation and cell proliferation arrest through specific activation of the MAP kinase pathway.
Involvement in disease
A chromosomal aberration involving ALK is found in a form of non-Hodgkin lymphoma. Translocation t(2;5)(p23;q35) with NPM1. The resulting chimeric NPM1-ALK protein homodimerize and the kinase becomes constitutively activated. The constitutively active fusion proteins are responsible for 5-10% of non-Hodgkin lymphomas.
A chromosomal aberration involving ALK is associated with inflammatory myofibroblastic tumors (IMTs). Translocation t(2;11)(p23;p15) with CARS; translocation t(2;4)(p23;q21) with SEC31A.
A chromosomal aberration involving ALK is associated with anaplastic large-cell lymphoma (ALCL). Translocation t(2;17)(p23;q25) with ALO17.
Neuroblastoma 3 (NBLST3): A common neoplasm of early childhood arising from embryonic cells that form the primitive neural crest and give rise to the adrenal medulla and the sympathetic nervous system.
Topology
Extracellular: 19-1038 aa
Helical: 1039-1059 aa
Cytoplasmic: 1060-1620 aa
PTM
Phosphorylated at tyrosine residues by autocatalysis, which activates kinase activity. In cells not stimulated by a ligand, receptor protein tyrosine phosphatase beta and zeta complex (PTPRB/PTPRZ1) dephosphorylates ALK at the sites in ALK that are undergoing autophosphorylation through autoactivation. Phosphorylation at Tyr-1507 is critical for SHC1 association.
N-glycosylated.
More Infomation

Woodling, N. S., Aleyakpo, B., Dyson, M. C., Minkley, L. J., Rajasingam, A., Dobson, A. J., ... & Partridge, L. (2020). The neuronal receptor tyrosine kinase Alk is a target for longevity. Aging Cell, 19(5), e13137.

Cho, B. C., Obermannova, R., Bearz, A., McKeage, M., Kim, D. W., Batra, U., ... & Dziadziuszko, R. (2019). Efficacy and safety of ceritinib (450 mg/d or 600 mg/d) with food versus 750-mg/d fasted in patients with ALK receptor tyrosine kinase (ALK)–positive NSCLC: primary efficacy results from the ASCEND-8 study. Journal of Thoracic Oncology, 14(7), 1255-1265.

Tabbò, F., D’Aveni, A., Tota, D., Pignataro, D., Bironzo, P., Carnio, S., ... & Novello, S. (2019). Pulmonary Arterial Hypertension in ALK Receptor Tyrosine Kinase–Positive Lung Cancer Patient: Adverse Event or Disease Spread?. Journal of Thoracic Oncology, 14(2), e38-e40.

Zhang, M., Wang, Q., Ding, Y., Wang, G., Chu, Y., He, X., ... & Lu, K. (2018). CUX1-ALK, a novel ALK rearrangement that responds to crizotinib in non–small cell lung cancer. Journal of Thoracic Oncology, 13(11), 1792-1797.

Huang, H. (2018). Anaplastic lymphoma kinase (ALK) receptor tyrosine kinase: a catalytic receptor with many faces. International journal of molecular sciences, 19(11), 3448.

Schrock, A. B., Zhu, V. W., Hsieh, W. S., Madison, R., Creelan, B., Silberberg, J., ... & Ou, S. H. I. (2018). Receptor tyrosine kinase fusions and BRAF kinase fusions are rare but actionable resistance mechanisms to EGFR tyrosine kinase inhibitors. Journal of Thoracic Oncology, 13(9), 1312-1323.

Gouzi, J. Y., Bouraimi, M., Roussou, I. G., Moressis, A., & Skoulakis, E. M. (2018). The Drosophila receptor tyrosine kinase alk constrains long-term memory formation. Journal of Neuroscience, 38(35), 7701-7712.

Mo, E. S., Cheng, Q., Reshetnyak, A. V., Schlessinger, J., & Nicoli, S. (2017). Alk and Ltk ligands are essential for iridophore development in zebrafish mediated by the receptor tyrosine kinase Ltk. Proceedings of the National Academy of Sciences, 114(45), 12027-12032.

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For research use only. Not intended for any clinical use.

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