白细胞介素-2

白细胞介素-2
已知的結構
PDB	直系同源搜索: 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
别名	IL2；, IL-2, TCGF, lymphokine, interleukin 2
外部ID	OMIM：147680 MGI：96548 HomoloGene：488 GeneCards：IL2
相關疾病
	过敏、1型糖尿病
基因位置（人类）
染色体	4號染色體
终止	122,456,725 bp
基因位置（小鼠）
染色体	小鼠3号染色体
终止	37,180,108 bp
RNA表达模式
	查阅更多表达数据
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; • 血浆蛋白结合;
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; • 适应性免疫; • 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; • 免疫反应; • 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

白细胞介素2 (英語：Interleukin 2，IL-2)是细胞因子中白细胞介素的一种，在免疫系统中起重要作用。它是一种蛋白质，负责调节白血球（白细胞，通常是淋巴细胞）的免疫活性。 IL-2的生成是机体受微生物感染时免疫应答的一部分，以区别“自己”与“非己”。IL-2通过与淋巴细胞表面的IL-2 受体结合来发挥作用。

信号通路

IL-2是拥有四个α螺旋束的细胞因子家族的一员，这一家族包括IL-4、IL-7、IL-9、IL-15和IL-21。IL-2的信号通过与之结合的IL-2受体传导到胞内，IL-2受体是由α、β、γ三条链组成的异聚体，其中γ链为本家族所有IL的受体共有^[6]。

当IL-2受体α亚基（IL-2RA）单独存在时，其与配体的亲和力只有完整的IL-2受体（包含了β、γ亚基）的百分之一，β和γ亚基的参与对IL-2R参与T细胞的信号转导是必要的^[7]。

历史

发现

作为免疫系统的一种水溶性分子，白细胞介素2是第一种被发现并被克隆的白细胞介素，其对应受体也是第一个被克隆并被解析结构的I型细胞因子受体。^[8]^:712

在1960年代中期，有研究报道了白细胞条件培养基中有促进淋巴细胞增殖的“活性因子”^[9]^:16。在1970年代中期，又发现了正常的人骨髓细胞可在某种条件性培养基中选择性的使T细胞扩增，此条件性培养基用由植物血凝素刺激人正常淋巴细胞而来^[8]^:712。这其中的关键因子被称为白细胞介素2，源自鼠细胞的白细胞介素2于1979年分离纯化，人细胞源的分离纯化于1980年^[10]。在多个实验室的激烈竞争中，人IL-2基因最终在1982年被克隆^[11]^:76。

应用

IL-2的促免疫活性使得其在20世纪八九十年代成为一种有希望进入医药市场的免疫增强药物。在1983年，Cetus公司制得了修饰重组的人IL-2蛋白（去掉了氨基端的丙氨酸，125号位的丝氨酸换为半胱氨酸）并冠以商品名Aldesleukin（后期改为Proleukin）^[11]^:76–77^[12]^:201^[13]。此后，安进公司也进入了这一领域，制得了自己的重组/突变蛋白，很快两家公司就对簿公堂，Cetus最终赢得了专利诉讼将安进逐出了此领域^[11]^:151。在1990年，Cetus的aldesleukin获得了九个欧洲国家的批准，但是在同年，美国食品药品监督管理局（FDA）拒绝了Cetus的aldesleukin上市申请^[14]。这一失利导致了Cetus公司的破产，并于1991年被Chiron公司收购^[15]^[16]。此后，Chiron公司继续开发IL-2，并在1992年以Proleukin为商品名获得了FDA的批准，用以治疗转移性的肾细胞癌^[17]。

截止1993年，Proleukin仍是唯一获得批准的IL-2药物，但此时罗氏公司也开发了自己的修饰的IL-2（在氨基端增加了甲硫氨酸）商品名为teceleukin，Glaxo公司也发展的新药bioleukin，在氨基端增加了甲硫氨酸，125号残基替换为丙氨酸。此后，又有数十种基于IL-2及联合其它免疫因子的病人血细胞刺激回输方法被开发出来^[13]^[18]。

参考文献

^ 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 （页面存档备份，存于互联网档案馆） 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]. （原始内容存档于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]. （原始内容存档于2021-12-02）.
^ Lehrman S. Cetus: A Collision Course With Failure. The Scientist Magazine. January 20, 1992 [2022-01-18]. （原始内容存档于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. （原始内容存档于2021-11-01）.

外部链接

Proleukin website （页面存档备份，存于互联网档案馆）
IL2 Resource Site
IL-2 Signaling Pathway （页面存档备份，存于互联网档案馆）

[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 （页面存档备份，存于互联网档案馆） 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]. （原始内容存档于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]. （原始内容存档于2021-12-02）.

[Lehrman_1992-16] Lehrman S. Cetus: A Collision Course With Failure. The Scientist Magazine. January 20, 1992 [2022-01-18]. （原始内容存档于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. （原始内容存档于2021-11-01）.

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