未分化リンパ腫キナーゼ

ALK
PDBに登録されている構造
PDB	オルソログ検索: RCSB PDBe PDBj
PDBのIDコード一覧
	2KUP, 2KUQ, 2XB7, 2XBA, 2XP2, 2YFX, 2YHV, 2YJR, 2YJS, 2YS5, 2YT2, 3AOX, 3L9P, 3LCS, 3LCT, 4ANL, 4ANQ, 4ANS, 4CCB, 4CCU, 4CD0, 4CLI, 4CLJ, 4CMO, 4CMT, 4CMU, 4CNH, 4CTB, 4CTC, 4DCE, 4FNW, 4FNX, 4FNY, 4FNZ, 4FOB, 4FOD, 4JOA, 4MKC, 4TT7, 4Z55, 5FTO, 5AAB, 5AAA, 5J7H, 5AA9, 5IUH, 5IUI, 5IMX, 5FTQ, 5A9U, 5IUG, 5AA8, 5AAC
識別子
記号	ALK, CD246, NBLST3, anaplastic lymphoma receptor tyrosine kinase, ALK receptor tyrosine kinase, ALK (gene), ALK1
外部ID	OMIM: 105590 MGI: 103305 HomoloGene: 68387 GeneCards: ALK
遺伝子の位置 (ヒト)
染色体	2番染色体 (ヒト)
終点	29,921,586 bp
遺伝子の位置 (マウス)
染色体	17番染色体 (マウス)
終点	72,911,622 bp
RNA発現パターン
	; ;
	さらなる参照発現データ
遺伝子オントロジー
分子機能	• トランスフェラーゼ活性; • ヌクレオチド結合; • protein kinase activity; • キナーゼ活性; • NF-kappaB-inducing kinase activity; • 血漿タンパク結合; • identical protein binding; • ATP binding; • transmembrane receptor protein tyrosine kinase activity; • protein tyrosine kinase activity;
細胞の構成要素	• integral component of membrane; • 膜; • エキソソーム; • integral component of plasma membrane; • 細胞内; • 細胞膜; • 高分子複合体; • receptor complex;
生物学的プロセス	• regulation of apoptotic process; • transmembrane receptor protein tyrosine kinase signaling pathway; • 神経系発生; • タンパク質リン酸化; • positive regulation of NF-kappaB transcription factor activity; • 細胞増殖; • 自己リン酸化; • シグナル伝達; • neuron development; • peptidyl-tyrosine phosphorylation; • NIK/NF-kappaB signaling; • リン酸化; • 脳発生; • 海馬発生; • adult behavior; • swimming behavior; • regulation of cell population proliferation; • regulation of dopamine receptor signaling pathway; • response to environmental enrichment; • regulation of neuron differentiation; • positive regulation of dendrite development;
	出典:Amigo / QuickGO
オルソログ
	238
	11682
	ENSG00000171094
	ENSMUSG00000055471
	Q9UM73
	P97793
	NM_004304; NM_001353765
	NM_007439
	NP_004295; NP_001340694
	NP_031465
	ウィキデータ
閲覧/編集ヒト	閲覧/編集マウス

未分化リンパ腫キナーゼ（みぶんかリンパしゅキナーゼ、英: anaplastic lymphoma kinase、略称: ALK）は、ヒトではALK遺伝子によってコードされている酵素である^[5]^[6]。ALK受容体型チロシンキナーゼやCD246としても知られる。

概要 ALK, PDBに登録されている構造 ...

閉じる

未分化リンパ腫キナーゼ（ALK）は、未分化大細胞リンパ腫（ALCL）細胞で1994年に発見された^[5]^[7]。ALCLはt(2;5)(p23;q35)染色体転座によってNPM-ALK融合タンパク質が産生されるようになることで引き起こされる。このタンパク質は、ヌクレオフォスミン（英語版）（NPM）タンパク質のN末端部分にALKのキナーゼドメインが融合したものである。NPM部分が二量体化することで、ALKキナーゼドメインは恒常的に活性化される^[5]^[7]。

ALKの全長タンパク質は1997年に2つのグループによって同定された^[8]^[9]。推測アミノ酸配列からALKは新規受容体型チロシンキナーゼ（RTK）であること、細胞外のリガンド結合ドメイン、膜貫通ドメイン、細胞内のチロシンキナーゼドメインを持つことが明らかにされた^[8]^[9]。ヒトALKのチロシンキナーゼドメインはインスリン受容体のものと高度に類似しているが、細胞外ドメインはRTKファミリー内で独特であり、2つのMAMドメイン（英語版）、LDLa（low-density lipoprotein receptor class A）ドメイン、グリシンリッチ領域を含んでいる^[9]^[10]。全体的な相同性に基づくとALKはLTK（英語版）と密接に関連しており、インスリン受容体ともにRTKスーパーファミリー内のサブグループを形成している^[8]^[9]。ヒトのALK遺伝子がコードするALKタンパク質は、1620アミノ酸、180 kDaである^[8]^[9]。

哺乳類での発見以降、ALKのオルソログはいくつか同定されており、2001年にはキイロショウジョウバエDrosphila melanogasterでdAlkが^[10]、2004年には線虫Caenorhabditis elegansでscd-2が^[11]、2013年にはゼブラフィッシュDanio rerioでDrAlkがそれぞれ発見されている^[12]。

ヒトのALK/LTK受容体のリガンドは2014年に同定された^[13]^[14]^[15]。FAM150A（AUGβ）、FAM150B（AUGα）と呼ばれる2つの小さな分泌ペプチドは、ALKシグナル伝達を強力に活性化する。ALKを活性化するリガンドは、ショウジョウバエではJeb（Jelly belly）^[16]^[17]、 C. elegansではHEN-1（hesitation behaviour 1）である^[18]。ゼブラフィッシュや他の脊椎動物ではリガンドは未報告である^[19]。

リガンドの結合後、全長のALK受容体は二量体化し、コンフォメーション変化を起こし、自身のキナーゼドメインを自己活性化し、そして他のALK受容体の特定のチロシン残基に対してトランスにリン酸化を行う。ALKのリン酸化残基はいくつかのアダプタータンパク質やその他の細胞内タンパク質をリクルートするための結合部位として機能する。リクルートされるタンパク質には、GRB2^[20]、IRS1^[20]^[21]、Shc（英語版）^[20]^[22]、Src^[23]、FRS2（英語版）^[22]、PTPN11/Shp2^[24]、PLCγ^[21]^[25]、PI3K^[21]^[26]、NF1（英語版）^[27]が含まれる。その他、ALKの下流の標的として報告されているものとしては、FOXO3a^[28]、CDKN1B/p27kip^[29]、サイクリンD2、NIPA（英語版）^[30]^[31]、RAC1^[32]、CDC42（英語版）^[33]、p130Cas（英語版）^[34]、SHP1（英語版）^[35]、PIKFYVE（英語版）^[36]などがある。

リン酸化されたALKは、MAPK-ERK経路（英語版）、PI3K-AKT経路（英語版）、PLCγ経路、CRKL（英語版）-C3G（英語版）経路、JAK-STAT経路など複数の下流のシグナル伝達経路を活性化する^[19]^[37]。

ALK受容体は細胞間コミュニケーションや神経系の正常な発生・機能に重要な役割を果たす^[6]。この観察は、マウスの胚発生時にALKのmRNAが神経系中で広く発現していることに基づいている^[8]^[9]^[38]。In vitroでの機能研究では、ALKの活性化によってPC12細胞（英語版）^[22]^[39]^[40]^[41]や神経芽腫細胞株^[21]の神経分化が促進されることが示されている。

ALKはショウジョウバエの胚発生に重要である。この受容体を欠くハエは、内臓筋の創始細胞を決定することができず致死となる^[16]^[17]^[42]。一方で、ALKノックアウトマウスは神経発生やテストステロン産生に欠陥がみられるものの生存は可能であり、ALKは発生過程に必須ではないことが示唆される^[43]^[44]^[45]。

ALKは網膜の軸索投射^[46]、成長とサイズ^[27]^[47]、神経筋接合部でのシナプスの形成^[48]^[49]、エタノールに対する行動反応^[50]^[51]^[52]^[53]、そして睡眠^[54]を調節している。ALKは学習と長期記憶を制限して制約をかけており、ALK受容体の低分子阻害剤によって学習^[27]と長期記憶^[55]を改善し、また健康寿命を延ばすことができる^[56]。ALKは低体重の候補遺伝子でもあり、遺伝的欠失は食事やレプチン変異による肥満に対する抵抗性をもたらす^[57]^{[注釈 1]}。

ALK遺伝子は、他の遺伝子との融合遺伝子の形成、遺伝子コピー数の増加、遺伝子をコードするDNAの変異という3通りの方法でがん遺伝子となる場合がある^[19]^[37]。

未分化大細胞リンパ腫

t(2;5)染色体転座は、未分化大細胞リンパ腫（ALCL）の約60%（ALK陽性未分化大細胞リンパ腫と稀な原発性皮膚未分化大細胞リンパ腫 [Primary cutaneous anaplastic large cell lymphoma]）と関係している。転座はALK遺伝子とNPM遺伝子の融合遺伝子を作り出し、2番染色体（英語版）に由来するALK遺伝子の3'部分（触媒ドメインをコードする）が5番染色体（英語版）のNPM遺伝子の5'部分へ融合する。NPM-ALK融合遺伝子の産物は発がん性である。ALCL患者の一部ではALKの3'部分がTPM3（英語版）遺伝子の5'配列へ融合している。稀なケースでは、ALKの5'側の融合パートナーはTFG（英語版）、ATIC（英語版）、CLTC（英語版）、TPM4（英語版）、MSN、ALO17、MYH9（英語版）などとなっている^[58]。

肺腺癌

EML4（英語版）-ALK融合遺伝子は、非小細胞肺癌（英語版）（NSCLC）の約3–5%の原因となっている。この症例の大部分は腺癌である。腫瘍中でこの遺伝子を検出する標準的な検査法は、蛍光in situハイブリダイゼーション（FISH）である。近年、Roche Ventanaの免疫組織化学による変異の検査法が中国とEUで承認された^[59]。ALK陽性肺がんは全ての年代の患者でみられるが、平均的には若い年代に多い傾向がある。ALK陽性肺がんは軽度喫煙者や非喫煙者でより一般的であるが、この病気の患者のかなりの数は喫煙者または元喫煙者である。NSCLCにおけるEML4-ALK再編成は排他的であり、EGFR変異型またはKRAS変異型の腫瘍ではみられない^[60]。

他の腫瘍における遺伝子再編成と過剰発現

神経芽腫の家族性症例^[61]
炎症性筋線維芽細胞性腫瘍（英語版）^[62]^[63]
成人^[64]^[65]または小児^[66]^[67]の腎細胞癌
食道扁平上皮癌^[68]^[69]
乳癌^[70]、特に炎症性のもの^[71]
結腸腺癌^[70]
膠芽腫^[72]^[73]
甲状腺未分化癌（英語版）^[74]

→詳細は「ALK阻害薬（英語版）」を参照

ザーコリ（クリゾチニブ）はファイザーによって生産され、2011年8月26日に末期肺がん治療に対するFDAの承認を受けた^[75]。ALK陽性肺がんの82人の患者で行われた第I相臨床試験の初期結果では、全奏効率は57%、8週間時点での病勢コントロール率は87%、6か月時点での無増悪生存率は72%であった。再発性または難治性ALK陽性ALCL患者では、クリゾチニブの客観的奏効率は65–90%、3年無増悪生存率は60–75%であった。最初の100日間の治療後、リンパ腫の再発は確認されていない。現時点では無期限で治療を継続する必要がある^[76]^[77]^[78]。

セリチニブは、クリゾチニブ抵抗性または不耐容性のALK陽性NSCLC患者に対する治療が2014年4月にFDAによって承認された^[79]。

エヌトレクチニブ（英語版）（RXDX-101）は、Ignytaによって開発された選択的チロシンキナーゼ阻害薬で、全てのTrk受容体（英語版）（NTRK）、ROS1（英語版）、ALKに対してnM濃度で特異性を示す。STARTRK-2と呼ばれる国際的な多施設非盲検第II相試験において、ROS1/NTRK/ALK遺伝子再編成を有する患者での薬剤の試験が行われている^[80]。

出典

[1]
GRCh38: Ensembl release 89: ENSG00000171094 - Ensembl, May 2017
[2]
GRCm38: Ensembl release 89: ENSMUSG00000055471 - Ensembl, May 2017
[3]
Human PubMed Reference:
[4]
Mouse PubMed Reference:
[5]
“Fusion of a kinase gene, ALK, to a nucleolar protein gene, NPM, in non-Hodgkin's lymphoma”. Science 263 (5151): 1281–4. (March 1994). Bibcode: 1994Sci...263.1281M. doi:10.1126/science.8122112. PMID 8122112.
[6]
“Entrez Gene: ALK anaplastic lymphoma kinase (Ki-1)”. 2022年8月28日閲覧。
[7]
“Hyperphosphorylation of a novel 80 kDa protein-tyrosine kinase similar to Ltk in a human Ki-1 lymphoma cell line, AMS3”. Oncogene 9 (6): 1567–74. (June 1994). PMID 8183550.
[8]
“Molecular characterization of ALK, a receptor tyrosine kinase expressed specifically in the nervous system”. Oncogene 14 (4): 439–49. (January 1997). doi:10.1038/sj.onc.1200849. PMID 9053841.
[9]
“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. (May 1997). doi:10.1038/sj.onc.1201062. PMID 9174053.
[10]
“Identification and characterization of DAlk: a novel Drosophila melanogaster RTK which drives ERK activation in vivo”. Genes to Cells 6 (6): 531–44. (June 2001). doi:10.1046/j.1365-2443.2001.00440.x. PMC 1975818. PMID 11442633.
[11]
“An SCF-like ubiquitin ligase complex that controls presynaptic differentiation”. Nature 430 (6997): 345–50. (July 2004). Bibcode: 2004Natur.430..345L. doi:10.1038/nature02647. PMID 15208641.
[12]
“Anaplastic lymphoma kinase is required for neurogenesis in the developing central nervous system of zebrafish”. PLOS ONE 8 (5): e63757. (May 2013). Bibcode: 2013PLoSO...863757Y. doi:10.1371/journal.pone.0063757. PMC 3648509. PMID 23667670.
[13]
“FAM150A and FAM150B are activating ligands for anaplastic lymphoma kinase”. eLife 4: e09811. (September 2015). doi:10.7554/eLife.09811. PMC 4658194. PMID 26418745.
[14]
“Augmentor α and β (FAM150) are ligands of the receptor tyrosine kinases ALK and LTK: Hierarchy and specificity of ligand-receptor interactions”. Proceedings of the National Academy of Sciences of the United States of America 112 (52): 15862–7. (December 2015). Bibcode: 2015PNAS..11215862R. doi:10.1073/pnas.1520099112. PMC 4702955. PMID 26630010.
[15]
“Deorphanization of the human leukocyte tyrosine kinase (LTK) receptor by a signaling screen of the extracellular proteome”. Proceedings of the National Academy of Sciences of the United States of America 111 (44): 15741–5. (November 2014). Bibcode: 2014PNAS..11115741Z. doi:10.1073/pnas.1412009111. PMC 4226105. PMID 25331893.
[16]
“Jeb signals through the Alk receptor tyrosine kinase to drive visceral muscle fusion”. Nature 425 (6957): 512–6. (October 2003). Bibcode: 2003Natur.425..512E. doi:10.1038/nature01950. PMID 14523447.
[17]
“Jelly belly protein activates the receptor tyrosine kinase Alk to specify visceral muscle pioneers”. Nature 425 (6957): 507–12. (October 2003). Bibcode: 2003Natur.425..507L. doi:10.1038/nature01916. PMID 14523446.
[18]
“C. elegans anaplastic lymphoma kinase ortholog SCD-2 controls dauer formation by modulating TGF-beta signaling”. Current Biology 18 (15): 1101–9. (August 2008). doi:10.1016/j.cub.2008.06.060. PMC 3489285. PMID 18674914.
[19]
“Mechanistic insight into ALK receptor tyrosine kinase in human cancer biology”. Nature Reviews. Cancer 13 (10): 685–700. (October 2013). doi:10.1038/nrc3580. PMID 24060861.
[20]
“Characterization of the transforming activity of p80, a hyperphosphorylated protein in a Ki-1 lymphoma cell line with chromosomal translocation t(2;5)”. Proceedings of the National Academy of Sciences of the United States of America 93 (9): 4181–6. (April 1996). Bibcode: 1996PNAS...93.4181F. doi:10.1073/pnas.93.9.4181. PMC 39508. PMID 8633037.
[21]
“ALK receptor tyrosine kinase promotes cell growth and neurite outgrowth”. Journal of Cell Science 117 (Pt 15): 3319–29. (July 2004). doi:10.1242/jcs.01183. PMID 15226403.
[22]
“ALK activation induces Shc and FRS2 recruitment: Signaling and phenotypic outcomes in PC12 cells differentiation”. FEBS Letters 581 (4): 727–34. (February 2007). doi:10.1016/j.febslet.2007.01.039. PMID 17274988.
[23]
“Nucleophosmin-anaplastic lymphoma kinase of anaplastic large-cell lymphoma recruits, activates, and uses pp60c-src to mediate its mitogenicity”. Blood 103 (4): 1464–71. (February 2004). doi:10.1182/blood-2003-04-1038. PMID 14563642.
[24]
“The tyrosine phosphatase Shp2 interacts with NPM-ALK and regulates anaplastic lymphoma cell growth and migration”. Cancer Research 67 (9): 4278–86. (May 2007). doi:10.1158/0008-5472.CAN-06-4350. PMID 17483340.
[25]
“Nucleophosmin-anaplastic lymphoma kinase of large-cell anaplastic lymphoma is a constitutively active tyrosine kinase that utilizes phospholipase C-gamma to mediate its mitogenicity”. Molecular and Cellular Biology 18 (12): 6951–61. (December 1998). doi:10.1128/mcb.18.12.6951. PMC 109278. PMID 9819383.
[26]
“Nucleophosmin-anaplastic lymphoma kinase associated with anaplastic large-cell lymphoma activates the phosphatidylinositol 3-kinase/Akt antiapoptotic signaling pathway”. Blood 96 (13): 4319–27. (December 2000). doi:10.1182/blood.v96.13.4319.h8004319_4319_4327. PMID 11110708.
[27]
“The receptor tyrosine kinase Alk controls neurofibromin functions in Drosophila growth and learning”. PLOS Genetics 7 (9): e1002281. (September 2011). doi:10.1371/journal.pgen.1002281. PMC 3174217. PMID 21949657.
[28]
“NPM-ALK fusion kinase of anaplastic large-cell lymphoma regulates survival and proliferative signaling through modulation of FOXO3a”. Blood 103 (12): 4622–9. (June 2004). doi:10.1182/blood-2003-03-0820. PMID 14962911.
[29]
“Inhibition of Akt increases p27Kip1 levels and induces cell cycle arrest in anaplastic large cell lymphoma”. Blood 105 (2): 827–9. (January 2005). doi:10.1182/blood-2004-06-2125. PMC 1382060. PMID 15374880.
[30]
“Identification and characterization of a nuclear interacting partner of anaplastic lymphoma kinase (NIPA)”. The Journal of Biological Chemistry 278 (32): 30028–36. (August 2003). doi:10.1074/jbc.M300883200. PMID 12748172.
[31]
“NIPA defines an SCF-type mammalian E3 ligase that regulates mitotic entry”. Cell 122 (1): 45–57. (July 2005). doi:10.1016/j.cell.2005.04.034. PMID 16009132.
[32]
“Activation of Rac1 and the exchange factor Vav3 are involved in NPM-ALK signaling in anaplastic large cell lymphomas”. Oncogene 27 (19): 2728–36. (April 2008). doi:10.1038/sj.onc.1210921. PMID 17998938.
[33]
“The anaplastic lymphoma kinase controls cell shape and growth of anaplastic large cell lymphoma through Cdc42 activation”. Cancer Research 68 (21): 8899–907. (November 2008). doi:10.1158/0008-5472.CAN-08-2568. PMC 2596920. PMID 18974134.
[34]
“p130Cas mediates the transforming properties of the anaplastic lymphoma kinase”. Blood 106 (12): 3907–16. (December 2005). doi:10.1182/blood-2005-03-1204. PMC 1895100. PMID 16105984.
[35]
“The tyrosine 343 residue of nucleophosmin (NPM)-anaplastic lymphoma kinase (ALK) is important for its interaction with SHP1, a cytoplasmic tyrosine phosphatase with tumor suppressor functions”. The Journal of Biological Chemistry 285 (26): 19813–20. (June 2010). doi:10.1074/jbc.M110.121988. PMC 2888392. PMID 20424160.
[36]
“The nucleophosmin-anaplastic lymphoma kinase oncogene interacts, activates, and uses the kinase PIKfyve to increase invasiveness”. The Journal of Biological Chemistry 286 (37): 32105–14. (September 2011). doi:10.1074/jbc.M111.227512. PMC 3173219. PMID 21737449.
[37]
“Anaplastic lymphoma kinase: signalling in development and disease”. The Biochemical Journal 420 (3): 345–61. (May 2009). doi:10.1042/BJ20090387. PMC 2708929. PMID 19459784.
[38]
“Characterization of the expression of the ALK receptor tyrosine kinase in mice”. Gene Expression Patterns 6 (5): 448–61. (June 2006). doi:10.1016/j.modgep.2005.11.006. PMID 16458083.
[39]
“Activation of anaplastic lymphoma kinase receptor tyrosine kinase induces neuronal differentiation through the mitogen-activated protein kinase pathway”. The Journal of Biological Chemistry 276 (12): 9526–31. (March 2001). doi:10.1074/jbc.M007333200. PMID 11121404.
[40]
“Activation and inhibition of anaplastic lymphoma kinase receptor tyrosine kinase by monoclonal antibodies and absence of agonist activity of pleiotrophin”. The Journal of Biological Chemistry 280 (28): 26039–48. (July 2005). doi:10.1074/jbc.M501972200. PMID 15886198.
[41]
“Role of the subcellular localization of ALK tyrosine kinase domain in neuronal differentiation of PC12 cells”. Journal of Cell Science 118 (Pt 24): 5811–23. (December 2005). doi:10.1242/jcs.02695. PMID 16317043.
[42]
“Myoblast determination in the somatic and visceral mesoderm depends on Notch signalling as well as on milliways(mili(Alk)) as receptor for Jeb signalling”. Development 131 (4): 743–54. (February 2004). doi:10.1242/dev.00972. PMID 14757637.
[43]
“Behavioral and neurochemical alterations in mice deficient in anaplastic lymphoma kinase suggest therapeutic potential for psychiatric indications”. Neuropsychopharmacology 33 (3): 685–700. (February 2008). doi:10.1038/sj.npp.1301446. PMID 17487225.
[44]
“Anaplastic lymphoma kinase and leukocyte tyrosine kinase: functions and genetic interactions in learning, memory and adult neurogenesis”. Pharmacology, Biochemistry, and Behavior 100 (3): 566–74. (January 2012). doi:10.1016/j.pbb.2011.10.024. PMID 22079349.
[45]
“Targeted Disruption of ALK Reveals a Potential Role in Hypogonadotropic Hypogonadism”. PLOS ONE 10 (5): e0123542. (May 2015). Bibcode: 2015PLoSO..1023542W. doi:10.1371/journal.pone.0123542. PMC 4425494. PMID 25955180.
[46]
“Anterograde Jelly belly and Alk receptor tyrosine kinase signaling mediates retinal axon targeting in Drosophila”. Cell 128 (5): 961–75. (March 2007). doi:10.1016/j.cell.2007.02.024. PMID 17350579.
[47]
“Anaplastic lymphoma kinase spares organ growth during nutrient restriction in Drosophila”. Cell 146 (3): 435–47. (August 2011). doi:10.1016/j.cell.2011.06.040. PMID 21816278.
[48]
“Anterograde Jelly belly ligand to Alk receptor signaling at developing synapses is regulated by Mind the gap”. Development 137 (20): 3523–33. (October 2010). doi:10.1242/dev.047878. PMC 2947762. PMID 20876658.
[49]
“Jelly Belly trans-synaptic signaling to anaplastic lymphoma kinase regulates neurotransmission strength and synapse architecture”. Developmental Neurobiology 73 (3): 189–208. (March 2013). doi:10.1002/dneu.22056. PMC 3565053. PMID 22949158.
[50]
“An evolutionary conserved role for anaplastic lymphoma kinase in behavioral responses to ethanol”. PLOS ONE 6 (7): e22636. (Jul 2011). Bibcode: 2011PLoSO...622636L. doi:10.1371/journal.pone.0022636. PMC 3142173. PMID 21799923.
[51]
“Dependence-induced ethanol drinking and GABA neurotransmission are altered in Alk deficient mice”. Neuropharmacology 107: 1–8. (August 2016). doi:10.1016/j.neuropharm.2016.03.003. PMC 4912883. PMID 26946429.
[52]
“Anaplastic lymphoma kinase regulates binge-like drinking and dopamine receptor sensitivity in the ventral tegmental area”. Addiction Biology 22 (3): 665–678. (May 2017). doi:10.1111/adb.12358. PMC 4940304. PMID 26752591.
[53]
“Anaplastic Lymphoma Kinase Is a Regulator of Alcohol Consumption and Excitatory Synaptic Plasticity in the Nucleus Accumbens Shell”. Frontiers in Pharmacology 8: 533. (Aug 2017). doi:10.3389/fphar.2017.00533. PMC 5559467. PMID 28860990.
[54]
“Anaplastic Lymphoma Kinase Acts in the Drosophila Mushroom Body to Negatively Regulate Sleep”. PLOS Genetics 11 (11): e1005611. (November 2015). doi:10.1371/journal.pgen.1005611. PMC 4633181. PMID 26536237.
[55]
“Drosophila Receptor Tyrosine Kinase Alk Constrains Long-Term Memory Formation”. The Journal of Neuroscience 38 (35): 7701–7712. (August 2018). doi:10.1523/JNEUROSCI.0784-18.2018. PMC 6705970. PMID 30030398.
[56]
“The neuronal receptor tyrosine kinase Alk is a target for longevity”. Aging Cell e13137 (5): e13137. (April 2020). doi:10.1111/acel.13137. PMC 7253064. PMID 32291952.
[57]
“Identification of ALK in Thinness”. Cell 13:S0092-8674 (20): 30497–9. (21 May 2020). doi:10.1016/j.cell.2020.04.034. PMID 32442405.
[58]
“Inhibitors of the anaplastic lymphoma kinase”. Expert Opinion on Investigational Drugs 21 (7): 985–94. (July 2012). doi:10.1517/13543784.2012.690031. PMID 22612599.
[59]
“VENTANA ALK (D5F3) CDx Assay”. Diagnostics. 2022年9月3日閲覧。
[60]
“International association for the study of lung cancer/american thoracic society/european respiratory society international multidisciplinary classification of lung adenocarcinoma”. Journal of Thoracic Oncology 6 (2): 244–85. (February 2011). doi:10.1097/JTO.0b013e318206a221. PMC 4513953. PMID 21252716.
[61]
“Identification of ALK as a major familial neuroblastoma predisposition gene”. Nature 455 (7215): 930–5. (October 2008). Bibcode: 2008Natur.455..930M. doi:10.1038/nature07261. PMC 2672043. PMID 18724359.
[62]
“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. (August 2002). doi:10.1002/gcc.10033. PMID 12112524.
[63]
“TPM3-ALK and TPM4-ALK oncogenes in inflammatory myofibroblastic tumors”. The American Journal of Pathology 157 (2): 377–84. (August 2000). doi:10.1016/S0002-9440(10)64550-6. PMC 1850130. PMID 10934142.
[64]
“ALK alterations in adult renal cell carcinoma: frequency, clinicopathologic features and outcome in a large series of consecutively treated patients”. Modern Pathology 25 (11): 1516–25. (November 2012). doi:10.1038/modpathol.2012.107. PMID 22743654.
[65]
“Identification of anaplastic lymphoma kinase fusions in renal cancer: large-scale immunohistochemical screening by the intercalated antibody-enhanced polymer method”. Cancer 118 (18): 4427–36. (September 2012). doi:10.1002/cncr.27391. PMID 22252991.
[66]
“Renal cell carcinoma with novel VCL-ALK fusion: new representative of ALK-associated tumor spectrum”. Modern Pathology 24 (3): 430–42. (March 2011). doi:10.1038/modpathol.2010.213. PMID 21076462.
[67]
“ALK rearrangement in sickle cell trait-associated renal medullary carcinoma”. Genes, Chromosomes & Cancer 50 (3): 146–53. (March 2011). doi:10.1002/gcc.20839. PMID 21213368.
[68]
“Identification of squamous cell carcinoma associated proteins by proteomics and loss of beta tropomyosin expression in esophageal cancer”. World Journal of Gastroenterology 12 (44): 7104–12. (November 2006). doi:10.3748/wjg.v12.i44.7104. PMC 4087770. PMID 17131471.
[69]
“Primary oesophageal Ki (CD30)-positive ALK+ anaplastic large cell lymphoma of T-cell phenotype”. Singapore Medical Journal 49 (10): e289-92. (October 2008). PMID 18946602.
[70]
“Exon array profiling detects EML4-ALK fusion in breast, colorectal, and non-small cell lung cancers”. Molecular Cancer Research 7 (9): 1466–76. (September 2009). doi:10.1158/1541-7786.MCR-08-0522. PMID 19737969.
[71]
“ALK gene amplified in most inflammatory breast cancers”. Journal of the National Cancer Institute 104 (2): 87–8. (January 2012). doi:10.1093/jnci/djr553. PMID 22215853.
[72]
“Pleiotrophin signaling through anaplastic lymphoma kinase is rate-limiting for glioblastoma growth”. The Journal of Biological Chemistry 277 (16): 14153–8. (April 2002). doi:10.1074/jbc.M112354200. PMID 11809760.
[73]
“Identification of anaplastic lymphoma kinase as a receptor for the growth factor pleiotrophin”. The Journal of Biological Chemistry 276 (20): 16772–9. (May 2001). doi:10.1074/jbc.M010660200. PMID 11278720.
[74]
“Anaplastic thyroid cancers harbor novel oncogenic mutations of the ALK gene”. Cancer Research 71 (13): 4403–11. (July 2011). doi:10.1158/0008-5472.CAN-10-4041. PMC 3129369. PMID 21596819.
[75]
“Xalkori Approved for Lung Cancer”. FDA. 2022年9月3日閲覧。
[76]
Gambacorti-Passerini CB, Dilda I, Giudici G, Perego A, Pavesi F, Guerra L, et al. Clinical activity of crizotinib in advanced, chemoresistant ALK+ lymphoma patients. 2010 Annual Meeting of the American Society of Hematology. Orlando, Florida.
[77]
“Crizotinib in anaplastic large-cell lymphoma”. The New England Journal of Medicine 364 (8): 775–6. (February 2011). doi:10.1056/NEJMc1013224. PMID 21345110.
[78]
“Crizotinib in advanced, chemoresistant anaplastic lymphoma kinase-positive lymphoma patients”. Journal of the National Cancer Institute 106 (2): djt378. (February 2014). doi:10.1093/jnci/djt378. PMID 24491302.
[79]
“ZYKADIA (ceritinib) capsules, for oral use Initial U.S. Approval: 2014”. United States Food and Drug Administration. 2022年9月3日閲覧。
[80]
“A Clinical Trial for Many Kinds of Advanced Cancers | STARTRK-2 Trial”. web.archive.org (2016年8月12日). 2022年9月3日閲覧。

注釈

[注 1]
2020年に発表された、Estonian Genome Center of the University of Tartu （EGCUT）バイオバンクの47,102人を対象としたゲノムワイド関連解析研究（GWAS）では、BMIの下位6%に位置する健常人のDNAと平均的健常人のDNAとの比較が行われた。この研究では、痩せと関係したALK遺伝子の遺伝的多型が同定された。次の段階として行われたマウスやショウジョウバエでの実験では、ALKホモログをノックアウトしたマウスは食事レベルは正常であるものの、幼時から成体になるまで脂肪や体重が少ないことが示された。ALKの阻害は、この遺伝子と関係したがんに対する化学療法として既に着目されているが、体重増加の防止の方法にもなる可能性がある。

“ALK-positive lymphoma: a single disease with a broad spectrum of morphology”. Blood 91 (6): 2076–84. (March 1998). doi:10.1182/blood.V91.6.2076. PMID 9490693.
“The emerging normal and disease-related roles of anaplastic lymphoma kinase”. Cellular and Molecular Life Sciences 61 (23): 2939–53. (December 2004). doi:10.1007/s00018-004-4275-9. PMID 15583856.
“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. (November 1999). doi:10.1182/blood.V94.9.3265. PMID 10556217.
“The cytoplasmic truncated receptor tyrosine kinase ALK homodimer immortalizes and cooperates with ras in cellular transformation”. FASEB Journal 15 (8): 1416–8. (June 2001). doi:10.1096/fj.00-0678fje. PMID 11387242.
“Anaplastic lymphoma kinase (ALK) activates Stat3 and protects hematopoietic cells from cell death”. Oncogene 21 (7): 1038–47. (February 2002). doi:10.1038/sj.onc.1205152. PMID 11850821.
“ALK as a novel lymphoma-associated tumor antigen: identification of 2 HLA-A2.1-restricted CD8+ T-cell epitopes”. Blood 99 (6): 2100–6. (March 2002). doi:10.1182/blood.V99.6.2100. PMID 11877285.
“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 Research 62 (5): 1559–66. (March 2002). PMID 11888936.
“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”. The American Journal of Pathology 160 (4): 1487–94. (April 2002). doi:10.1016/S0002-9440(10)62574-6. PMC 1867210. PMID 11943732.
“Expression levels of apoptosis-related proteins predict clinical outcome in anaplastic large cell lymphoma”. Blood 99 (12): 4540–6. (June 2002). doi:10.1182/blood.V99.12.4540. PMID 12036886.
“Expression and functional analysis of the anaplastic lymphoma kinase (ALK) gene in tumor cell lines”. International Journal of Cancer 100 (1): 49–56. (July 2002). doi:10.1002/ijc.10435. PMID 12115586.

ALK protein, human - MeSH・アメリカ国立医学図書館・生命科学用語シソーラス（英語）
ALK Correlations, Experiments, Publications and Clinical Trials
GeneReviews/NCBI/NIH/UW entry on ALK-Related Neuroblastoma Susceptibility
OMIM entries on ALK-Related Neuroblastoma Susceptibility
Human ALK genome location and ALK gene details page in the UCSC Genome Browser.

[refGRCh38Ensembl-1] [1]
GRCh38: Ensembl release 89: ENSG00000171094 - Ensembl, May 2017

[refGRCm38Ensembl-2] [2]
GRCm38: Ensembl release 89: ENSMUSG00000055471 - Ensembl, May 2017

[3] [3]
Human PubMed Reference:

[4] [4]
Mouse PubMed Reference:

[pmid8122112-5] [5]
“Fusion of a kinase gene, ALK, to a nucleolar protein gene, NPM, in non-Hodgkin's lymphoma”. Science 263 (5151): 1281–4. (March 1994). Bibcode: 1994Sci...263.1281M. doi:10.1126/science.8122112. PMID 8122112.

[entrez-6] [6]
“Entrez Gene: ALK anaplastic lymphoma kinase (Ki-1)”. 2022年8月28日閲覧。

[:13-7] [7]
“Hyperphosphorylation of a novel 80 kDa protein-tyrosine kinase similar to Ltk in a human Ki-1 lymphoma cell line, AMS3”. Oncogene 9 (6): 1567–74. (June 1994). PMID 8183550.

[:0-8] [8]
“Molecular characterization of ALK, a receptor tyrosine kinase expressed specifically in the nervous system”. Oncogene 14 (4): 439–49. (January 1997). doi:10.1038/sj.onc.1200849. PMID 9053841.

[:1-9] [9]
“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. (May 1997). doi:10.1038/sj.onc.1201062. PMID 9174053.

[:2-10] [10]
“Identification and characterization of DAlk: a novel Drosophila melanogaster RTK which drives ERK activation in vivo”. Genes to Cells 6 (6): 531–44. (June 2001). doi:10.1046/j.1365-2443.2001.00440.x. PMC 1975818. PMID 11442633.

[An_SCF-like_ubiquitin_ligase_comple-11] [11]
“An SCF-like ubiquitin ligase complex that controls presynaptic differentiation”. Nature 430 (6997): 345–50. (July 2004). Bibcode: 2004Natur.430..345L. doi:10.1038/nature02647. PMID 15208641.

[:14-12] [12]
“Anaplastic lymphoma kinase is required for neurogenesis in the developing central nervous system of zebrafish”. PLOS ONE 8 (5): e63757. (May 2013). Bibcode: 2013PLoSO...863757Y. doi:10.1371/journal.pone.0063757. PMC 3648509. PMID 23667670.

[:15-13] [13]
“FAM150A and FAM150B are activating ligands for anaplastic lymphoma kinase”. eLife 4: e09811. (September 2015). doi:10.7554/eLife.09811. PMC 4658194. PMID 26418745.

[:16-14] [14]
“Augmentor α and β (FAM150) are ligands of the receptor tyrosine kinases ALK and LTK: Hierarchy and specificity of ligand-receptor interactions”. Proceedings of the National Academy of Sciences of the United States of America 112 (52): 15862–7. (December 2015). Bibcode: 2015PNAS..11215862R. doi:10.1073/pnas.1520099112. PMC 4702955. PMID 26630010.

[:17-15] [15]
“Deorphanization of the human leukocyte tyrosine kinase (LTK) receptor by a signaling screen of the extracellular proteome”. Proceedings of the National Academy of Sciences of the United States of America 111 (44): 15741–5. (November 2014). Bibcode: 2014PNAS..11115741Z. doi:10.1073/pnas.1412009111. PMC 4226105. PMID 25331893.

[:3-16] [16]
“Jeb signals through the Alk receptor tyrosine kinase to drive visceral muscle fusion”. Nature 425 (6957): 512–6. (October 2003). Bibcode: 2003Natur.425..512E. doi:10.1038/nature01950. PMID 14523447.

[:4-17] [17]
“Jelly belly protein activates the receptor tyrosine kinase Alk to specify visceral muscle pioneers”. Nature 425 (6957): 507–12. (October 2003). Bibcode: 2003Natur.425..507L. doi:10.1038/nature01916. PMID 14523446.

[:18-18] [18]
“C. elegans anaplastic lymphoma kinase ortholog SCD-2 controls dauer formation by modulating TGF-beta signaling”. Current Biology 18 (15): 1101–9. (August 2008). doi:10.1016/j.cub.2008.06.060. PMC 3489285. PMID 18674914.

[:10-19] [19]
“Mechanistic insight into ALK receptor tyrosine kinase in human cancer biology”. Nature Reviews. Cancer 13 (10): 685–700. (October 2013). doi:10.1038/nrc3580. PMID 24060861.

[:5-20] [20]
“Characterization of the transforming activity of p80, a hyperphosphorylated protein in a Ki-1 lymphoma cell line with chromosomal translocation t(2;5)”. Proceedings of the National Academy of Sciences of the United States of America 93 (9): 4181–6. (April 1996). Bibcode: 1996PNAS...93.4181F. doi:10.1073/pnas.93.9.4181. PMC 39508. PMID 8633037.

[:6-21] [21]
“ALK receptor tyrosine kinase promotes cell growth and neurite outgrowth”. Journal of Cell Science 117 (Pt 15): 3319–29. (July 2004). doi:10.1242/jcs.01183. PMID 15226403.

[:7-22] [22]
“ALK activation induces Shc and FRS2 recruitment: Signaling and phenotypic outcomes in PC12 cells differentiation”. FEBS Letters 581 (4): 727–34. (February 2007). doi:10.1016/j.febslet.2007.01.039. PMID 17274988.

[:19-23] [23]
“Nucleophosmin-anaplastic lymphoma kinase of anaplastic large-cell lymphoma recruits, activates, and uses pp60c-src to mediate its mitogenicity”. Blood 103 (4): 1464–71. (February 2004). doi:10.1182/blood-2003-04-1038. PMID 14563642.

[:20-24] [24]
“The tyrosine phosphatase Shp2 interacts with NPM-ALK and regulates anaplastic lymphoma cell growth and migration”. Cancer Research 67 (9): 4278–86. (May 2007). doi:10.1158/0008-5472.CAN-06-4350. PMID 17483340.

[:21-25] [25]
“Nucleophosmin-anaplastic lymphoma kinase of large-cell anaplastic lymphoma is a constitutively active tyrosine kinase that utilizes phospholipase C-gamma to mediate its mitogenicity”. Molecular and Cellular Biology 18 (12): 6951–61. (December 1998). doi:10.1128/mcb.18.12.6951. PMC 109278. PMID 9819383.

[:22-26] [26]
“Nucleophosmin-anaplastic lymphoma kinase associated with anaplastic large-cell lymphoma activates the phosphatidylinositol 3-kinase/Akt antiapoptotic signaling pathway”. Blood 96 (13): 4319–27. (December 2000). doi:10.1182/blood.v96.13.4319.h8004319_4319_4327. PMID 11110708.

[:8-27] [27]
“The receptor tyrosine kinase Alk controls neurofibromin functions in Drosophila growth and learning”. PLOS Genetics 7 (9): e1002281. (September 2011). doi:10.1371/journal.pgen.1002281. PMC 3174217. PMID 21949657.

[:23-28] [28]
“NPM-ALK fusion kinase of anaplastic large-cell lymphoma regulates survival and proliferative signaling through modulation of FOXO3a”. Blood 103 (12): 4622–9. (June 2004). doi:10.1182/blood-2003-03-0820. PMID 14962911.

[:24-29] [29]
“Inhibition of Akt increases p27Kip1 levels and induces cell cycle arrest in anaplastic large cell lymphoma”. Blood 105 (2): 827–9. (January 2005). doi:10.1182/blood-2004-06-2125. PMC 1382060. PMID 15374880.

[:25-30] [30]
“Identification and characterization of a nuclear interacting partner of anaplastic lymphoma kinase (NIPA)”. The Journal of Biological Chemistry 278 (32): 30028–36. (August 2003). doi:10.1074/jbc.M300883200. PMID 12748172.

[:26-31] [31]
“NIPA defines an SCF-type mammalian E3 ligase that regulates mitotic entry”. Cell 122 (1): 45–57. (July 2005). doi:10.1016/j.cell.2005.04.034. PMID 16009132.

[:27-32] [32]
“Activation of Rac1 and the exchange factor Vav3 are involved in NPM-ALK signaling in anaplastic large cell lymphomas”. Oncogene 27 (19): 2728–36. (April 2008). doi:10.1038/sj.onc.1210921. PMID 17998938.

[:28-33] [33]
“The anaplastic lymphoma kinase controls cell shape and growth of anaplastic large cell lymphoma through Cdc42 activation”. Cancer Research 68 (21): 8899–907. (November 2008). doi:10.1158/0008-5472.CAN-08-2568. PMC 2596920. PMID 18974134.

[:29-34] [34]
“p130Cas mediates the transforming properties of the anaplastic lymphoma kinase”. Blood 106 (12): 3907–16. (December 2005). doi:10.1182/blood-2005-03-1204. PMC 1895100. PMID 16105984.

[:30-35] [35]
“The tyrosine 343 residue of nucleophosmin (NPM)-anaplastic lymphoma kinase (ALK) is important for its interaction with SHP1, a cytoplasmic tyrosine phosphatase with tumor suppressor functions”. The Journal of Biological Chemistry 285 (26): 19813–20. (June 2010). doi:10.1074/jbc.M110.121988. PMC 2888392. PMID 20424160.

[:31-36] [36]
“The nucleophosmin-anaplastic lymphoma kinase oncogene interacts, activates, and uses the kinase PIKfyve to increase invasiveness”. The Journal of Biological Chemistry 286 (37): 32105–14. (September 2011). doi:10.1074/jbc.M111.227512. PMC 3173219. PMID 21737449.

[:9-37] [37]
“Anaplastic lymphoma kinase: signalling in development and disease”. The Biochemical Journal 420 (3): 345–61. (May 2009). doi:10.1042/BJ20090387. PMC 2708929. PMID 19459784.

[:32-38] [38]
“Characterization of the expression of the ALK receptor tyrosine kinase in mice”. Gene Expression Patterns 6 (5): 448–61. (June 2006). doi:10.1016/j.modgep.2005.11.006. PMID 16458083.

[:33-39] [39]
“Activation of anaplastic lymphoma kinase receptor tyrosine kinase induces neuronal differentiation through the mitogen-activated protein kinase pathway”. The Journal of Biological Chemistry 276 (12): 9526–31. (March 2001). doi:10.1074/jbc.M007333200. PMID 11121404.

[:34-40] [40]
“Activation and inhibition of anaplastic lymphoma kinase receptor tyrosine kinase by monoclonal antibodies and absence of agonist activity of pleiotrophin”. The Journal of Biological Chemistry 280 (28): 26039–48. (July 2005). doi:10.1074/jbc.M501972200. PMID 15886198.

[:35-41] [41]
“Role of the subcellular localization of ALK tyrosine kinase domain in neuronal differentiation of PC12 cells”. Journal of Cell Science 118 (Pt 24): 5811–23. (December 2005). doi:10.1242/jcs.02695. PMID 16317043.

[:36-42] [42]
“Myoblast determination in the somatic and visceral mesoderm depends on Notch signalling as well as on milliways(mili(Alk)) as receptor for Jeb signalling”. Development 131 (4): 743–54. (February 2004). doi:10.1242/dev.00972. PMID 14757637.

[:37-43] [43]
“Behavioral and neurochemical alterations in mice deficient in anaplastic lymphoma kinase suggest therapeutic potential for psychiatric indications”. Neuropsychopharmacology 33 (3): 685–700. (February 2008). doi:10.1038/sj.npp.1301446. PMID 17487225.

[:11-44] [44]
“Anaplastic lymphoma kinase and leukocyte tyrosine kinase: functions and genetic interactions in learning, memory and adult neurogenesis”. Pharmacology, Biochemistry, and Behavior 100 (3): 566–74. (January 2012). doi:10.1016/j.pbb.2011.10.024. PMID 22079349.

[:38-45] [45]
“Targeted Disruption of ALK Reveals a Potential Role in Hypogonadotropic Hypogonadism”. PLOS ONE 10 (5): e0123542. (May 2015). Bibcode: 2015PLoSO..1023542W. doi:10.1371/journal.pone.0123542. PMC 4425494. PMID 25955180.

[:39-46] [46]
“Anterograde Jelly belly and Alk receptor tyrosine kinase signaling mediates retinal axon targeting in Drosophila”. Cell 128 (5): 961–75. (March 2007). doi:10.1016/j.cell.2007.02.024. PMID 17350579.

[:40-47] [47]
“Anaplastic lymphoma kinase spares organ growth during nutrient restriction in Drosophila”. Cell 146 (3): 435–47. (August 2011). doi:10.1016/j.cell.2011.06.040. PMID 21816278.

[:41-48] [48]
“Anterograde Jelly belly ligand to Alk receptor signaling at developing synapses is regulated by Mind the gap”. Development 137 (20): 3523–33. (October 2010). doi:10.1242/dev.047878. PMC 2947762. PMID 20876658.

[:42-49] [49]
“Jelly Belly trans-synaptic signaling to anaplastic lymphoma kinase regulates neurotransmission strength and synapse architecture”. Developmental Neurobiology 73 (3): 189–208. (March 2013). doi:10.1002/dneu.22056. PMC 3565053. PMID 22949158.

[:43-50] [50]
“An evolutionary conserved role for anaplastic lymphoma kinase in behavioral responses to ethanol”. PLOS ONE 6 (7): e22636. (Jul 2011). Bibcode: 2011PLoSO...622636L. doi:10.1371/journal.pone.0022636. PMC 3142173. PMID 21799923.

[:44-51] [51]
“Dependence-induced ethanol drinking and GABA neurotransmission are altered in Alk deficient mice”. Neuropharmacology 107: 1–8. (August 2016). doi:10.1016/j.neuropharm.2016.03.003. PMC 4912883. PMID 26946429.

[:45-52] [52]
“Anaplastic lymphoma kinase regulates binge-like drinking and dopamine receptor sensitivity in the ventral tegmental area”. Addiction Biology 22 (3): 665–678. (May 2017). doi:10.1111/adb.12358. PMC 4940304. PMID 26752591.

[:46-53] [53]
“Anaplastic Lymphoma Kinase Is a Regulator of Alcohol Consumption and Excitatory Synaptic Plasticity in the Nucleus Accumbens Shell”. Frontiers in Pharmacology 8: 533. (Aug 2017). doi:10.3389/fphar.2017.00533. PMC 5559467. PMID 28860990.

[:47-54] [54]
“Anaplastic Lymphoma Kinase Acts in the Drosophila Mushroom Body to Negatively Regulate Sleep”. PLOS Genetics 11 (11): e1005611. (November 2015). doi:10.1371/journal.pgen.1005611. PMC 4633181. PMID 26536237.

[:12-55] [55]
“Drosophila Receptor Tyrosine Kinase Alk Constrains Long-Term Memory Formation”. The Journal of Neuroscience 38 (35): 7701–7712. (August 2018). doi:10.1523/JNEUROSCI.0784-18.2018. PMC 6705970. PMID 30030398.

[:48-56] [56]
“The neuronal receptor tyrosine kinase Alk is a target for longevity”. Aging Cell e13137 (5): e13137. (April 2020). doi:10.1111/acel.13137. PMC 7253064. PMID 32291952.

[:49-57] [57]
“Identification of ALK in Thinness”. Cell 13:S0092-8674 (20): 30497–9. (21 May 2020). doi:10.1016/j.cell.2020.04.034. PMID 32442405.

[pmid22612599-59] [58]
“Inhibitors of the anaplastic lymphoma kinase”. Expert Opinion on Investigational Drugs 21 (7): 985–94. (July 2012). doi:10.1517/13543784.2012.690031. PMID 22612599.

[:50-60] [59]
“VENTANA ALK (D5F3) CDx Assay”. Diagnostics. 2022年9月3日閲覧。

[pmid21252716-61] [60]
“International association for the study of lung cancer/american thoracic society/european respiratory society international multidisciplinary classification of lung adenocarcinoma”. Journal of Thoracic Oncology 6 (2): 244–85. (February 2011). doi:10.1097/JTO.0b013e318206a221. PMC 4513953. PMID 21252716.

[pmid18724359-62] [61]
“Identification of ALK as a major familial neuroblastoma predisposition gene”. Nature 455 (7215): 930–5. (October 2008). Bibcode: 2008Natur.455..930M. doi:10.1038/nature07261. PMC 2672043. PMID 18724359.

[pmid12112524-63] [62]
“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. (August 2002). doi:10.1002/gcc.10033. PMID 12112524.

[pmid10934142-64] [63]
“TPM3-ALK and TPM4-ALK oncogenes in inflammatory myofibroblastic tumors”. The American Journal of Pathology 157 (2): 377–84. (August 2000). doi:10.1016/S0002-9440(10)64550-6. PMC 1850130. PMID 10934142.

[pmid22743654-65] [64]
“ALK alterations in adult renal cell carcinoma: frequency, clinicopathologic features and outcome in a large series of consecutively treated patients”. Modern Pathology 25 (11): 1516–25. (November 2012). doi:10.1038/modpathol.2012.107. PMID 22743654.

[pmid22252991-66] [65]
“Identification of anaplastic lymphoma kinase fusions in renal cancer: large-scale immunohistochemical screening by the intercalated antibody-enhanced polymer method”. Cancer 118 (18): 4427–36. (September 2012). doi:10.1002/cncr.27391. PMID 22252991.

[pmid21076462-67] [66]
“Renal cell carcinoma with novel VCL-ALK fusion: new representative of ALK-associated tumor spectrum”. Modern Pathology 24 (3): 430–42. (March 2011). doi:10.1038/modpathol.2010.213. PMID 21076462.

[pmid21213368-68] [67]
“ALK rearrangement in sickle cell trait-associated renal medullary carcinoma”. Genes, Chromosomes & Cancer 50 (3): 146–53. (March 2011). doi:10.1002/gcc.20839. PMID 21213368.

[pmid17131471-69] [68]
“Identification of squamous cell carcinoma associated proteins by proteomics and loss of beta tropomyosin expression in esophageal cancer”. World Journal of Gastroenterology 12 (44): 7104–12. (November 2006). doi:10.3748/wjg.v12.i44.7104. PMC 4087770. PMID 17131471.

[pmid18946602-70] [69]
“Primary oesophageal Ki (CD30)-positive ALK+ anaplastic large cell lymphoma of T-cell phenotype”. Singapore Medical Journal 49 (10): e289-92. (October 2008). PMID 18946602.

[exon-71] [70]
“Exon array profiling detects EML4-ALK fusion in breast, colorectal, and non-small cell lung cancers”. Molecular Cancer Research 7 (9): 1466–76. (September 2009). doi:10.1158/1541-7786.MCR-08-0522. PMID 19737969.

[pmid22215853-72] [71]
“ALK gene amplified in most inflammatory breast cancers”. Journal of the National Cancer Institute 104 (2): 87–8. (January 2012). doi:10.1093/jnci/djr553. PMID 22215853.

[pmid11809760-73] [72]
“Pleiotrophin signaling through anaplastic lymphoma kinase is rate-limiting for glioblastoma growth”. The Journal of Biological Chemistry 277 (16): 14153–8. (April 2002). doi:10.1074/jbc.M112354200. PMID 11809760.

[pmid11278720-74] [73]
“Identification of anaplastic lymphoma kinase as a receptor for the growth factor pleiotrophin”. The Journal of Biological Chemistry 276 (20): 16772–9. (May 2001). doi:10.1074/jbc.M010660200. PMID 11278720.

[pmid21596819-75] [74]
“Anaplastic thyroid cancers harbor novel oncogenic mutations of the ALK gene”. Cancer Research 71 (13): 4403–11. (July 2011). doi:10.1158/0008-5472.CAN-10-4041. PMC 3129369. PMID 21596819.

[:51-76] [75]
“Xalkori Approved for Lung Cancer”. FDA. 2022年9月3日閲覧。

[:52-77] [76]
Gambacorti-Passerini CB, Dilda I, Giudici G, Perego A, Pavesi F, Guerra L, et al. Clinical activity of crizotinib in advanced, chemoresistant ALK+ lymphoma patients. 2010 Annual Meeting of the American Society of Hematology. Orlando, Florida.

[Gambacorti-Passerini_2011-78] [77]
“Crizotinib in anaplastic large-cell lymphoma”. The New England Journal of Medicine 364 (8): 775–6. (February 2011). doi:10.1056/NEJMc1013224. PMID 21345110.

[Gambacorti-Passerini_2014-79] [78]
“Crizotinib in advanced, chemoresistant anaplastic lymphoma kinase-positive lymphoma patients”. Journal of the National Cancer Institute 106 (2): djt378. (February 2014). doi:10.1093/jnci/djt378. PMID 24491302.

[urlwww.accessdata.fda.gov-80] [79]
“ZYKADIA (ceritinib) capsules, for oral use Initial U.S. Approval: 2014”. United States Food and Drug Administration. 2022年9月3日閲覧。

[81] [80]
“A Clinical Trial for Many Kinds of Advanced Cancers | STARTRK-2 Trial”. web.archive.org (2016年8月12日). 2022年9月3日閲覧。

[:0-58] [注 1]
2020年に発表された、Estonian Genome Center of the University of Tartu （EGCUT）バイオバンクの47,102人を対象としたゲノムワイド関連解析研究（GWAS）では、BMIの下位6%に位置する健常人のDNAと平均的健常人のDNAとの比較が行われた。この研究では、痩せと関係したALK遺伝子の遺伝的多型が同定された。次の段階として行われたマウスやショウジョウバエでの実験では、ALKホモログをノックアウトしたマウスは食事レベルは正常であるものの、幼時から成体になるまで脂肪や体重が少ないことが示された。ALKの阻害は、この遺伝子と関係したがんに対する化学療法として既に着目されているが、体重増加の防止の方法にもなる可能性がある。

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未分化大細胞リンパ腫

肺腺癌

他の腫瘍における遺伝子再編成と過剰発現

出典

注釈

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未分化リンパ腫キナーゼ

未分化大細胞リンパ腫

肺腺癌

他の腫瘍における遺伝子再編成と過剰発現

出典

注釈

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同定

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機能

病理

ALK阻害薬

出典と注釈

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