白血球介素-2

白血球介素-2
已知的結構
PDB	直系同源搜尋: PDBe RCSB
PDBID列表
	1IRL、1M47、1M48、1M49、1M4A、1M4B、1M4C、1NBP、1PW6、1PY2、1QVN、1Z92、2B5I、2ERJ、3QAZ、3QB1、3INK、4NEJ、4NEM
識別號
別名	IL2；, IL-2, TCGF, lymphokine, interleukin 2
外部ID	OMIM：147680 MGI：96548 HomoloGene：488 GeneCards：IL2
相關疾病
	過敏、一型糖尿病
基因位置（人類）
染色體	4號染色體
終止	122,456,725 bp
基因位置（小鼠）
染色體	小鼠3號染色體
終止	37,180,108 bp
RNA表達模式
	查閱更多表達數據
基因本體
分子功能	• 細胞因子活性; • interleukin-2 receptor binding; • glycosphingolipid binding; • kinase activator activity; • 生長因子活性; • kappa-type opioid receptor binding; • carbohydrate binding; • 血漿蛋白結合;
細胞組分	• 細胞外區域; • 胞內; • 細胞外空間;
生物學過程	• positive regulation of T cell differentiation; • negative regulation of protein phosphorylation; • G protein-coupled receptor signaling pathway; • positive regulation of protein phosphorylation; • positive regulation of inflammatory response; • 適應性免疫; • negative regulation of heart contraction; • immune system process; • positive regulation of cytosolic calcium ion concentration; • positive regulation of regulatory T cell differentiation; • cell-cell signaling; • positive regulation of interferon-gamma production; • natural killer cell activation; • negative regulation of apoptotic process; • positive regulation of dendritic spine development; • negative regulation of lymphocyte proliferation; • MAPK cascade; • regulation of T cell homeostatic proliferation; • T cell differentiation; • positive regulation of cell growth; • protein kinase C-activating G protein-coupled receptor signaling pathway; • 細胞粘附; • positive regulation of B cell proliferation; • positive regulation of tissue remodeling; • positive regulation of T cell proliferation; • 免疫反應; • positive regulation of cell population proliferation; • extrinsic apoptotic signaling pathway in absence of ligand; • negative regulation of B cell apoptotic process; • positive regulation of isotype switching to IgG isotypes; • positive regulation of interleukin-17 production; • response to ethanol; • negative regulation of inflammatory response; • positive regulation of transcription by RNA polymerase II; • positive regulation of activated T cell proliferation; • negative regulation of T-helper 17 cell differentiation; • leukocyte activation involved in immune response; • positive regulation of tyrosine phosphorylation of STAT protein; • regulation of regulatory T cell differentiation; • regulation of signaling receptor activity; • cytokine-mediated signaling pathway; • interleukin-2-mediated signaling pathway; • positive regulation of kinase activity;
	Sources:Amigo / QuickGO
直系同源
	3558
	16183
	ENSG00000109471
	ENSMUSG00000027720
	P60568
	P04351
	NM_000586
	NM_008366
	NP_000577
	NP_032392
	維基數據
檢視/編輯人類	檢視/編輯小鼠

白血球介素2 (英語：Interleukin 2，IL-2)是細胞因子中白血球介素的一種，在免疫系統中起重要作用。它是一種蛋白質，負責調節白血球（白血球，通常是淋巴細胞）的免疫活性。 IL-2的生成是機體受微生物感染時免疫應答的一部分，以區別「自己」與「非己」。IL-2通過與淋巴細胞表面的IL-2 受體結合來發揮作用。

信號通路

IL-2是擁有四個α螺旋束的細胞因子家族的一員，這一家族包括IL-4、IL-7、IL-9、IL-15和IL-21。IL-2的信號通過與之結合的IL-2受體傳導到胞內，IL-2受體是由α、β、γ三條鏈組成的異聚體，其中γ鏈為本家族所有IL的受體共有^[6]。

當IL-2受體α亞基（IL-2RA）單獨存在時，其與配體的親和力只有完整的IL-2受體（包含了β、γ亞基）的百分之一，β和γ亞基的參與對IL-2R參與T細胞的信號轉導是必要的^[7]。

歷史

發現

作為免疫系統的一種水溶性分子，白血球介素2是第一種被發現並被克隆的白血球介素，其對應受體也是第一個被克隆並被解析結構的I型細胞因子受體。^[8]^:712

在1960年代中期，有研究報道了白血球條件培養基中有促進淋巴細胞增殖的「活性因子」^[9]^:16。在1970年代中期，又發現了正常的人骨髓細胞可在某種條件性培養基中選擇性的使T細胞擴增，此條件性培養基用由植物血凝素刺激人正常淋巴細胞而來^[8]^:712。這其中的關鍵因子被稱為白血球介素2，源自鼠細胞的白血球介素2於1979年分離純化，人細胞源的分離純化於1980年^[10]。在多個實驗室的激烈競爭中，人IL-2基因最終在1982年被克隆^[11]^:76。

應用

IL-2的促免疫活性使得其在20世紀八九十年代成為一種有希望進入醫藥市場的免疫增強藥物。在1983年，Cetus公司製得了修飾重組的人IL-2蛋白（去掉了氨基端的丙氨酸，125號位的絲氨酸換為半胱氨酸）並冠以商品名Aldesleukin（後期改為Proleukin）^[11]^:76–77^[12]^:201^[13]。此後，安進公司也進入了這一領域，製得了自己的重組/突變蛋白，很快兩家公司就對簿公堂，Cetus最終贏得了專利訴訟將安進逐出了此領域^[11]^:151。在1990年，Cetus的aldesleukin獲得了九個歐洲國家的批准，但是在同年，美國食品藥品監督管理局（FDA）拒絕了Cetus的aldesleukin上市申請^[14]。這一失利導致了Cetus公司的破產，並於1991年被Chiron公司收購^[15]^[16]。此後，Chiron公司繼續開發IL-2，並在1992年以Proleukin為商品名獲得了FDA的批准，用以治療轉移性的腎細胞癌^[17]。

截止1993年，Proleukin仍是唯一獲得批准的IL-2藥物，但此時羅氏公司也開發了自己的修飾的IL-2（在氨基端增加了甲硫氨酸）商品名為teceleukin，Glaxo公司也發展的新藥bioleukin，在氨基端增加了甲硫氨酸，125號殘基替換為丙氨酸。此後，又有數十種基於IL-2及聯合其它免疫因子的病人血球刺激回輸方法被開發出來^[13]^[18]。

參考文獻

^ 與白细胞介素-2相關的疾病；在維基數據上查看/編輯參考.
^ ^2.0 ^2.1 ^2.2 GRCh38: Ensembl release 89: ENSG00000109471 - Ensembl, May 2017
^ ^3.0 ^3.1 ^3.2 GRCm38: Ensembl release 89: ENSMUSG00000027720 - Ensembl, May 2017
^ Human PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.
^ Mouse PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.
^ Liao W, Lin JX, Leonard WJ. IL-2 family cytokines: new insights into the complex roles of IL-2 as a broad regulator of T helper cell differentiation. Current Opinion in Immunology. October 2011, 23 (5): 598–604. PMC 3405730  . PMID 21889323. doi:10.1016/j.coi.2011.08.003.
^ Gaffen SL, Liu KD. Overview of interleukin-2 function, production and clinical applications. Cytokine. November 2004, 28 (3): 109–23. PMID 15473953. doi:10.1016/j.cyto.2004.06.010.
^ ^8.0 ^8.1 Paul WE. Fundamental immunology 6th. Philadelphia: Wolters Kluwer/Lippincott Williams & Wilkins. 2008. ISBN 978-0-7817-6519-0.
^ Chavez AR, Buchser W, Basse PH, Liang X, Appleman LJ, Maranchie JK, Zeh H, de Vera ME, Lotze MT. Pharmacologic administration of interleukin-2. Annals of the New York Academy of Sciences. December 2009, 1182: 14–27. PMID 20074271. doi:10.1111/j.1749-6632.2009.05160.x.
^ Welte K, Wang CY, Mertelsmann R, Venuta S, Feldman SP, Moore MA. Purification of human interleukin 2 to apparent homogeneity and its molecular heterogeneity. The Journal of Experimental Medicine. August 1982, 156 (2): 454–64. PMC 2186775  . PMID 6980256. doi:10.1084/jem.156.2.454.
^ ^11.0 ^11.1 ^11.2 Rabinow P. Making PCR: A story of biotechnology Paperback. Chicago, IL, USA: University of Chicago Press. 1997. ISBN 978-0226701479.
^ Hugo Almeida. Drugs obtained by biotechnology processing （頁面存檔備份，存於互聯網檔案館） Brazilian Journal of Pharmaceutical Sciences apr/jun 2011 47(2):199-207
^ ^13.0 ^13.1 Whittington R, Faulds D. Interleukin-2. A review of its pharmacological properties and therapeutic use in patients with cancer. Drugs. September 1993, 46 (3): 446–514. PMID 7693434. doi:10.2165/00003495-199346030-00009.
^ Pollack A. Cetus Drug Is Blocked By F.D.A.. New York Times. July 31, 1990 [2017-06-25]. （原始內容存檔於2020-09-28）. This source mentions approval in 9 European countries.
^ 2 Biotech Pioneers To Merge. New York Times. July 23, 1991 [2017-06-25]. （原始內容存檔於2021-12-02）.
^ Lehrman S. Cetus: A Collision Course With Failure. The Scientist Magazine. January 20, 1992 [2022-01-18]. （原始內容存檔於2016-08-05）.
^ Dutcher JP. Current status of interleukin-2 therapy for metastatic renal cell carcinoma and metastatic melanoma. Oncology. November 2002, 16 (11 Suppl 13): 4–10. PMID 12469934.
^ D02749 (Teceleukin). KEGG drug. （原始內容存檔於2021-11-01）.

外部連結

Proleukin website （頁面存檔備份，存於互聯網檔案館）
IL2 Resource Site
IL-2 Signaling Pathway （頁面存檔備份，存於互聯網檔案館）

[1] 與白细胞介素-2相關的疾病；在維基數據上查看/編輯參考.

[refGRCh38Ensembl-2] 2.0 ^2.1 ^2.2 GRCh38: Ensembl release 89: ENSG00000109471 - Ensembl, May 2017

[refGRCm38Ensembl-3] 3.0 ^3.1 ^3.2 GRCm38: Ensembl release 89: ENSMUSG00000027720 - Ensembl, May 2017

[4] Human PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.

[5] Mouse PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.

[Liao_2011-6] Liao W, Lin JX, Leonard WJ. IL-2 family cytokines: new insights into the complex roles of IL-2 as a broad regulator of T helper cell differentiation. Current Opinion in Immunology. October 2011, 23 (5): 598–604. PMC 3405730  . PMID 21889323. doi:10.1016/j.coi.2011.08.003.

[Gaffen_2004-7] Gaffen SL, Liu KD. Overview of interleukin-2 function, production and clinical applications. Cytokine. November 2004, 28 (3): 109–23. PMID 15473953. doi:10.1016/j.cyto.2004.06.010.

[Leonard-8] 8.0 ^8.1 Paul WE. Fundamental immunology 6th. Philadelphia: Wolters Kluwer/Lippincott Williams & Wilkins. 2008. ISBN 978-0-7817-6519-0.

[pmid20074271-9] Chavez AR, Buchser W, Basse PH, Liang X, Appleman LJ, Maranchie JK, Zeh H, de Vera ME, Lotze MT. Pharmacologic administration of interleukin-2. Annals of the New York Academy of Sciences. December 2009, 1182: 14–27. PMID 20074271. doi:10.1111/j.1749-6632.2009.05160.x.

[pmid6980256-10] Welte K, Wang CY, Mertelsmann R, Venuta S, Feldman SP, Moore MA. Purification of human interleukin 2 to apparent homogeneity and its molecular heterogeneity. The Journal of Experimental Medicine. August 1982, 156 (2): 454–64. PMC 2186775  . PMID 6980256. doi:10.1084/jem.156.2.454.

[CetusHist-11] 11.0 ^11.1 ^11.2 Rabinow P. Making PCR: A story of biotechnology Paperback. Chicago, IL, USA: University of Chicago Press. 1997. ISBN 978-0226701479.

[12] Hugo Almeida. Drugs obtained by biotechnology processing （頁面存檔備份，存於互聯網檔案館） Brazilian Journal of Pharmaceutical Sciences apr/jun 2011 47(2):199-207

[Whittington_1993-13] 13.0 ^13.1 Whittington R, Faulds D. Interleukin-2. A review of its pharmacological properties and therapeutic use in patients with cancer. Drugs. September 1993, 46 (3): 446–514. PMID 7693434. doi:10.2165/00003495-199346030-00009.

[Pollack_1990-14] Pollack A. Cetus Drug Is Blocked By F.D.A.. New York Times. July 31, 1990 [2017-06-25]. （原始內容存檔於2020-09-28）. This source mentions approval in 9 European countries.

[Pollack_1991-15] 2 Biotech Pioneers To Merge. New York Times. July 23, 1991 [2017-06-25]. （原始內容存檔於2021-12-02）.

[Lehrman_1992-16] Lehrman S. Cetus: A Collision Course With Failure. The Scientist Magazine. January 20, 1992 [2022-01-18]. （原始內容存檔於2016-08-05）.

[pmid12469934-17] Dutcher JP. Current status of interleukin-2 therapy for metastatic renal cell carcinoma and metastatic melanoma. Oncology. November 2002, 16 (11 Suppl 13): 4–10. PMID 12469934.

[urlKEGG_DRUG:_D02749-18] D02749 (Teceleukin). KEGG drug. （原始內容存檔於2021-11-01）.

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