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Anaplastic lymphoma kinase (Ki-1)
Identifiers
Symbols ALK; CD246; TFG/ALK
External IDs OMIM105590 MGI103305 HomoloGene68387 GeneCards: ALK Gene
RNA expression pattern
PBB GE ALK 208211 s at tn.png
PBB GE ALK 208212 s at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 238 11682
Ensembl ENSG00000171094 ENSMUSG00000055471
UniProt Q9UM73 P97793
RefSeq (mRNA) NM_004304 NM_007439
RefSeq (protein) NP_004295 NP_031465
Location (UCSC) Chr 2:
29.27 - 30 Mb
Chr 17:
71.77 - 72.51 Mb
PubMed search [1] [2]

ALK tyrosine kinase receptor is an enzyme that in humans is encoded by the ALK gene.[1][2][1]

Contents

Function

The 2;5 chromosomal translocation is frequently associated with anaplastic large cell lymphomas (ALCLs). The translocation creates a fusion gene consisting of the ALK (anaplastic lymphoma kinase) gene and the nucleophosmin (NPM) gene: the 3' half of ALK, derived from chromosome 2, is fused to the 5' portion of NPM from chromosome 5. The product of the NPM-ALK fusion gene is oncogenic. The deduced amino acid sequences reveal that ALK is a novel receptor tyrosine kinase having a putative transmembrane domain and an extracellular domain. These sequences are absent in the product of the transforming NPM-ALK gene. ALK shows the greatest sequence similarity to LTK (leukocyte tyrosine kinase). ALK plays an important role in the development of the brain and exerts its effects on specific neurons in the nervous system.[2]

Disease linkage

Recent study shows that mutation of ALK "are strongly linked to out-of-control cell proliferation and neuroblastoma", a deadly childhood form of cancer.[3 ]

See also

References

  1. ^ a b Morris SW, Kirstein MN, Valentine MB, Dittmer KG, Shapiro DN, Saltman DL, Look AT (Apr 1994). "Fusion of a kinase gene, ALK, to a nucleolar protein gene, NPM, in non-Hodgkin's lymphoma". Science 263 (5151): 1281-4. PMID 8122112.  
  2. ^ a b "Entrez Gene: ALK anaplastic lymphoma kinase (Ki-1)". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=238.  
  3. ^ "Gene That Causes Childhood Cancer Neuroblastoma Is Found". PRNewswire-USNewswire. http://www.prnewswire.com/cgi-bin/micro_stories.pl?ACCT=159681&TICK=CHOP&STORY=/www/story/08-25-2008/0004872713&EDATE=Aug+25,+2008. Retrieved 2008-08-26.  

Further reading

  • Benharroch D, Meguerian-Bedoyan Z, Lamant L, et al. (1998). "ALK-positive lymphoma: a single disease with a broad spectrum of morphology.". Blood 91 (6): 2076–84. PMID 9490693.  
  • Pulford K, Lamant L, Espinos E, et al. (2005). "The emerging normal and disease-related roles of anaplastic lymphoma kinase.". Cell. Mol. Life Sci. 61 (23): 2939–53. doi:10.1007/s00018-004-4275-9. PMID 15583856.  
  • Fujimoto J, Shiota M, Iwahara T, et al. (1996). "Characterization of the transforming activity of p80, a hyperphosphorylated protein in a Ki-1 lymphoma cell line with chromosomal translocation t(2;5).". Proc. Natl. Acad. Sci. U.S.A. 93 (9): 4181–6. doi:10.1073/pnas.93.9.4181. PMID 8633037.  
  • Iwahara T, Fujimoto J, Wen D, et al. (1997). "Molecular characterization of ALK, a receptor tyrosine kinase expressed specifically in the nervous system.". Oncogene 14 (4): 439–49. doi:10.1038/sj.onc.1200849. PMID 9053841.  
  • Morris SW, Naeve C, Mathew P, et al. (1997). "ALK, the chromosome 2 gene locus altered by the t(2;5) in non-Hodgkin's lymphoma, encodes a novel neural receptor tyrosine kinase that is highly related to leukocyte tyrosine kinase (LTK)". Oncogene 14 (18): 2175–88. doi:10.1038/sj.onc.1201062. PMID 9174053.  
  • Bai RY, Dieter P, Peschel C, et al. (1998). "Nucleophosmin-anaplastic lymphoma kinase of large-cell anaplastic lymphoma is a constitutively active tyrosine kinase that utilizes phospholipase C-gamma to mediate its mitogenicity.". Mol. Cell. Biol. 18 (12): 6951–61. PMID 9819383.  
  • Hernández L, Pinyol M, Hernández S, et al. (1999). "TRK-fused gene (TFG) is a new partner of ALK in anaplastic large cell lymphoma producing two structurally different TFG-ALK translocations.". Blood 94 (9): 3265–8. PMID 10556217.  
  • Souttou B, Carvalho NB, Raulais D, Vigny M (2001). "Activation of anaplastic lymphoma kinase receptor tyrosine kinase induces neuronal differentiation through the mitogen-activated protein kinase pathway.". J. Biol. Chem. 276 (12): 9526–31. doi:10.1074/jbc.M007333200. PMID 11121404.  
  • Stoica GE, Kuo A, Aigner A, et al. (2001). "Identification of anaplastic lymphoma kinase as a receptor for the growth factor pleiotrophin.". J. Biol. Chem. 276 (20): 16772–9. doi:10.1074/jbc.M010660200. PMID 11278720.  
  • Simonitsch I, Polgar D, Hajek M, et al. (2001). "The cytoplasmic truncated receptor tyrosine kinase ALK homodimer immortalizes and cooperates with ras in cellular transformation.". Faseb J. 15 (8): 1416–8. PMID 11387242.  
  • Powers C, Aigner A, Stoica GE, et al. (2002). "Pleiotrophin signaling through anaplastic lymphoma kinase is rate-limiting for glioblastoma growth.". J. Biol. Chem. 277 (16): 14153–8. doi:10.1074/jbc.M112354200. PMID 11809760.  
  • Zamo A, Chiarle R, Piva R, et al. (2002). "Anaplastic lymphoma kinase (ALK) activates Stat3 and protects hematopoietic cells from cell death.". Oncogene 21 (7): 1038–47. doi:10.1038/sj.onc.1205152. PMID 11850821.  
  • Passoni L, Scardino A, Bertazzoli C, et al. (2002). "ALK as a novel lymphoma-associated tumor antigen: identification of 2 HLA-A2.1-restricted CD8+ T-cell epitopes.". Blood 99 (6): 2100–6. doi:10.1182/blood.V99.6.2100. PMID 11877285.  
  • Bonvini P, Gastaldi T, Falini B, Rosolen A (2002). "Nucleophosmin-anaplastic lymphoma kinase (NPM-ALK), a novel Hsp90-client tyrosine kinase: down-regulation of NPM-ALK expression and tyrosine phosphorylation in ALK(+) CD30(+) lymphoma cells by the Hsp90 antagonist 17-allylamino,17-demethoxygeldanamycin.". Cancer Res. 62 (5): 1559–66. PMID 11888936.  
  • Hernández L, Beà S, Bellosillo B, et al. (2002). "Diversity of genomic breakpoints in TFG-ALK translocations in anaplastic large cell lymphomas: identification of a new TFG-ALK(XL) chimeric gene with transforming activity.". Am. J. Pathol. 160 (4): 1487–94. PMID 11943732.  
  • ten Berge RL, Meijer CJ, Dukers DF, et al. (2002). "Expression levels of apoptosis-related proteins predict clinical outcome in anaplastic large cell lymphoma.". Blood 99 (12): 4540–6. doi:10.1182/blood.V99.12.4540. PMID 12036886.  
  • Cools J, Wlodarska I, Somers R, et al. (2002). "Identification of novel fusion partners of ALK, the anaplastic lymphoma kinase, in anaplastic large-cell lymphoma and inflammatory myofibroblastic tumor.". Genes Chromosomes Cancer 34 (4): 354–62. doi:10.1002/gcc.10033. PMID 12112524.  
  • Dirks WG, Fähnrich S, Lis Y, et al. (2002). "Expression and functional analysis of the anaplastic lymphoma kinase (ALK) gene in tumor cell lines.". Int. J. Cancer 100 (1): 49–56. doi:10.1002/ijc.10435. PMID 12115586.  

External links

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

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