CD22
CD22,名為分化簇-22(英語:cluster of differentiation-22),是成熟B細胞表面的一種跨膜受體,屬於SIGLEC家族。[4]
CD22 | |||||||||||||||||||||||||
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識別號 | |||||||||||||||||||||||||
別名 | CD22;, SIGLEC-2, SIGLEC2, CD22 molecule | ||||||||||||||||||||||||
外部ID | OMIM:107266 MGI:88322 HomoloGene:31052 GeneCards:CD22 | ||||||||||||||||||||||||
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直系同源 | |||||||||||||||||||||||||
物種 | 人類 | 小鼠 | |||||||||||||||||||||||
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mRNA序列 |
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蛋白序列 |
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基因位置(UCSC) | 無數據 | Chr 7: 30.56 – 30.58 Mb | |||||||||||||||||||||||
PubMed查找 | [2] | [3] | |||||||||||||||||||||||
維基數據 | |||||||||||||||||||||||||
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功能
編輯CD22表現於成熟B細胞的表面,也表現於少量未成熟B細胞的表面,其主要功能是避免免疫系統過度活化,可降低罹患自體免疫性疾病的風險。[5]
CD22是一種可高度特異性識別糖基化蛋白(如CD45)的跨膜蛋白,可通過N端的一個免疫球蛋白(Ig)結構域與唾液酸結合。因擁有Ig結構域,CD22也屬於免疫球蛋白超家族。人類體內,CD22主要功能為抑制B細胞表面受體的活化。另外,小鼠實驗的結果發現B細胞運輸至派亞氏淋巴叢的過程亦有CD22的參與。[6]
機制
編輯CD22是B細胞受體的一個輔助受體,其與連結在抗原B細胞受體表面的抗原連接後,自己會被磷酸化,進而活化一些磷酸酶以抑制免疫反應[7]。
蛋白質交互作用
編輯CD22經過實驗證明會與以下蛋白質產生交互作用:Grb2[8][9]、PTPN6[9][10][11][12][13]、LYN[8][11]、SHC1[8]和INPP5D[8]。
應用
編輯CD22也可能作為抗癌藥物的標的,美國國立衛生研究院正在測試一種名為BL22的免疫毒素,BL22是一種抗CD22的單株抗體,與CD22結合後可以進入細胞中,達到殺死細胞的效果,可能有助於治療某些種類的白血病[14]。另外一種針對CD22的單株抗體藥物Epratuzumab也正在測試中,可能有助於治療白血病與全身性紅斑狼瘡[15]。
參考文獻
編輯- ^ 1.0 1.1 1.2 GRCm38: Ensembl release 89: ENSMUSG00000030577 - 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.
- ^ Crocker PR, et al. Siglecs: a family of sialic-acid binding lectins. Glycobiology. February 1998, 8 (2): v. PMID 9498912. doi:10.1093/glycob/8.2.0.
- ^ Hatta; et al. Identification of the gene variations in human CD22. Immunogenetics. 1999, 49 (4): 280–286 [2018-08-15]. doi:10.1007/s002510050494. (原始內容存檔於2019-09-24).
- ^ Lee M, Kiefel H, LaJevic MD, Macauley MS, Kawashima H, O'Hara E, Pan J, Paulson JC, Butcher EC. Transcriptional programs of lymphoid tissue capillary and high endothelium reveal control mechanisms for lymphocyte homing. Nature Immunology. October 2014, 15 (10): 982–95. PMC 4222088 . PMID 25173345. doi:10.1038/ni.2983.
- ^ Dörner T, Shock A, Smith KG. CD22 and Autoimmune Disease 31 (5). International Reviews of Immunology. 2012. doi:10.3109/08830185.2012.709890.
- ^ 8.0 8.1 8.2 8.3 Poe JC, Fujimoto M, Jansen PJ, Miller AS, Tedder TF. CD22 forms a quaternary complex with SHIP, Grb2, and Shc. A pathway for regulation of B lymphocyte antigen receptor-induced calcium flux. The Journal of Biological Chemistry. June 2000, 275 (23): 17420–7. PMID 10748054. doi:10.1074/jbc.M001892200.
- ^ 9.0 9.1 Otipoby KL, Draves KE, Clark EA. CD22 regulates B cell receptor-mediated signals via two domains that independently recruit Grb2 and SHP-1. The Journal of Biological Chemistry. November 2001, 276 (47): 44315–22. PMID 11551923. doi:10.1074/jbc.M105446200.
- ^ Blasioli J, Paust S, Thomas ML. Definition of the sites of interaction between the protein tyrosine phosphatase SHP-1 and CD22. The Journal of Biological Chemistry. January 1999, 274 (4): 2303–7. PMID 9890995. doi:10.1074/jbc.274.4.2303.
- ^ 11.0 11.1 Greer SF, Justement LB. CD45 regulates tyrosine phosphorylation of CD22 and its association with the protein tyrosine phosphatase SHP-1. Journal of Immunology. May 1999, 162 (9): 5278–86. PMID 10228003.
- ^ Law CL, Sidorenko SP, Chandran KA, Zhao Z, Shen SH, Fischer EH, Clark EA. CD22 associates with protein tyrosine phosphatase 1C, Syk, and phospholipase C-gamma(1) upon B cell activation. The Journal of Experimental Medicine. February 1996, 183 (2): 547–60. PMC 2192439 . PMID 8627166. doi:10.1084/jem.183.2.547.
- ^ Adachi T, Wienands J, Wakabayashi C, Yakura H, Reth M, Tsubata T. SHP-1 requires inhibitory co-receptors to down-modulate B cell antigen receptor-mediated phosphorylation of cellular substrates. The Journal of Biological Chemistry. July 2001, 276 (28): 26648–55. PMID 11356834. doi:10.1074/jbc.M100997200.
- ^ BL22 Immunotoxin in Treating Patients Previously Treated With Cladribine for Hairy Cell Leukemia. ClinicalTrials.gov - U.S. National Institutes of Health. [2018-08-14]. (原始內容存檔於2007-10-07).
- ^ Epratuzumab. DrugBank. Canadian Institutes of Health Research. [2018-08-16]. (原始內容存檔於2016-03-04).