発現細胞

全ての造血細胞

分子量

180-240 kDa

機能

tyrosine phosphatase, augments sinnaling through antigen receptor of B and T cells, multiple isoforms result from alternative splicing

ファミリー

fibronectin type III

疾患との関連

ホジキンリンパ腫：CD45は発現していない。

PrepTutorEJDIC

certificate of deposit / (また『C.D.』)Civil Defense民間防衛

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/03/18 14:02:38」(JST)

wiki en

[Wiki en表示]

Protein tyrosine phosphatase, receptor type, C also known as PTPRC is an enzyme that, in humans, is encoded by the PTPRC gene.^[1] PTPRC is also known as CD45 antigen (CD stands for cluster of differentiation), which was originally called leukocyte common antigen.^[2]

Function

The protein encoded by this gene is a member of the protein tyrosine phosphatase (PTP) family. PTPs are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. This PTP contains an extracellular domain, a single transmembrane segment and two tandem intracytoplasmic catalytic domains, and thus belongs to receptor type PTP. This gene is specifically expressed in hematopoietic cells. This PTP has been shown to be an essential regulator of T- and B-cell antigen receptor signaling. It functions through either direct interaction with components of the antigen receptor complexes or by activating various Src family kinases required for the antigen receptor signaling. This PTP also suppresses JAK kinases, and, thus, functions as a negative regulator of cytokine receptor signaling. Four alternatively spliced transcripts variants of this gene, which encode distinct isoforms, have been reported.^[2]

It is a type I transmembrane protein that is in various forms present on all differentiated hematopoietic cells except erythrocytes and plasma cells that assists in the activation of those cells (a form of co-stimulation). It is expressed in lymphomas, B-cell chronic lymphocytic leukemia, hairy cell leukemia, and acute nonlymphocytic leukemia. A monoclonal antibody to CD45 is used in routine immunohistochemistry to differentiate between histological sections from lymphomas and carcinomas.^[3]

Isoforms

The CD45 family consists of multiple members that are all products of a single complex gene. This gene contains 34 exons and three exons of the primary transcripts are alternatively spliced to generate up to eight different mature mRNAs and after translation eight different protein products. These three exons generate the RA, RB and RC isoforms.

Various isoforms of CD45 exist: CD45RA, CD45RB, CD45RC, CD45RAB, CD45RAC, CD45RBC, CD45R0, CD45R (ABC). CD45RA is located on naive T cells and CD45R0 is located on memory T cells. CD45 is also highly glycosylated. CD45R is the longest protein and migrates at 200 kDa when isolated from T cells. B cells also express CD45R with heavier glycosylation, bringing the molecular weight to 220 kDa, hence the name B220; B cell isoform of 220 kDa. B220 expression is not restricted to B cells and can also be expressed on activated T cells, on a subset of dendritic cells and other antigen presenting cells.

Naive T lymphocytes express large CD45 isoforms and are usually positive for CD45RA. Activated and memory T lymphocytes express the shortest CD45 isoform, CD45R0, which lacks RA, RB and RC exons. This shortest isoform facilitates T cell activation.

The cytoplasmic domain of CD45 is one of the largest known and it has an intrinsic phosphatase activity that removes an inhibitory phosphate group on a tyrosine kinase called Lck (in T cells) or Lyn/Fyn/Lck (in B cells) and activates it.

Interactions

PTPRC has been shown to interact with LYN,^[4] Lck,^[5]^[6] SKAP1^[7] and GANAB.^[8]^[9]^[10]

CD45 has been recently shown to interact with the HCMV UL11 protein. This interaction results in functional paralysis of T cells.^[11]

Clinical importance

Stem cells of several varieties, including mesenchymal stem cells and hæmatopoietic stem cells are found in the bone marrow. If a clinician wishes to separate the two, the CD45 marker is used to distinguish the two stem cell types, as CD45 is found on all leukocytes.

Use as a congenic marker

There are two identifiable alleles of CD45 in mice: CD45.1 (Ly5.1) and CD45.2 (Ly5.2). These two types of CD45 are believed to be functionally identical. As such, they are routinely used in scientific research to allow identification of cells. For instance, leukocytes can be transferred from a CD45.1 donor mouse, into a CD45.2 host mouse, and can be subsequently identified due to their expression of CD45.1. This technique is also routinely used when generating chimeras. An alternative system is the used of CD90 (Thy1) alleles. The CD90.1/CD90.2 system is used in the same manner as the CD45.1/CD45.2 system.

References

^ Kaplan R, Morse B, Huebner K, et al (September 1990). "Cloning of three human tyrosine phosphatases reveals a multigene family of receptor-linked protein-tyrosine-phosphatases expressed in brain". Proc. Natl. Acad. Sci. U.S.A. 87 (18): 7000–4. doi:10.1073/pnas.87.18.7000. PMC 54670. PMID 2169617. http://www.pnas.org/cgi/pmidlookup?view=long&pmid=2169617.
^ ^a ^b "Entrez Gene: PTPRC protein tyrosine phosphatase, receptor type, C". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5788.
^ Leong, Anthony S-Y; Cooper, Kumarason; Leong, F Joel W-M (2003). Manual of Diagnostic Cytology (2 ed.). Greenwich Medical Media, Ltd.. pp. 121–124. ISBN 1-84110-100-1.
^ Brown VK, Ogle EW, Burkhardt AL, Rowley RB, Bolen JB, Justement LB (June 1994). "Multiple components of the B cell antigen receptor complex associate with the protein tyrosine phosphatase, CD45". J. Biol. Chem. 269 (25): 17238–44. PMID 7516335.
^ Koretzky GA, Kohmetscher M, Ross S (April 1993). "CD45-associated kinase activity requires lck but not T cell receptor expression in the Jurkat T cell line". J. Biol. Chem. 268 (12): 8958–64. PMID 8473339.
^ Ng DH, Watts JD, Aebersold R, Johnson P (January 1996). "Demonstration of a direct interaction between p56lck and the cytoplasmic domain of CD45 in vitro". J. Biol. Chem. 271 (3): 1295–300. doi:10.1074/jbc.271.3.1295. PMID 8576115.
^ Wu L, Fu J, Shen SH (April 2002). "SKAP55 coupled with CD45 positively regulates T-cell receptor-mediated gene transcription". Mol. Cell. Biol. 22 (8): 2673–86. doi:10.1128/MCB.22.8.2673-2686.2002. PMC 133720. PMID 11909961. //www.ncbi.nlm.nih.gov/pmc/articles/PMC133720/.
^ Arendt CW, Ostergaard HL (May 1997). "Identification of the CD45-associated 116-kDa and 80-kDa proteins as the alpha- and beta-subunits of alpha-glucosidase II". J. Biol. Chem. 272 (20): 13117–25. doi:10.1074/jbc.272.20.13117. PMID 9148925.
^ Baldwin TA, Gogela-Spehar M, Ostergaard HL (October 2000). "Specific isoforms of the resident endoplasmic reticulum protein glucosidase II associate with the CD45 protein-tyrosine phosphatase via a lectin-like interaction". J. Biol. Chem. 275 (41): 32071–6. doi:10.1074/jbc.M003088200. PMID 10921916.
^ Baldwin TA, Ostergaard HL (October 2001). "Developmentally regulated changes in glucosidase II association with, and carbohydrate content of, the protein tyrosine phosphatase CD45". J. Immunol. 167 (7): 3829–35. PMID 11564800.
^ Gabaev I, Steinbrück L, Pokoyski C, Pich A, Stanton RJ, Schwinzer R, Schulz TF, Jacobs R, Messerle M, Kay-Fedorov PC (December 2011). "The human cytomegalovirus UL11 protein interacts with the receptor tyrosine phosphatase CD45, resulting in functional paralysis of T cells". PLoS Pathog. 7 (12): e1002432. doi:10.1371/journal.ppat.1002432. PMC 3234252. PMID 22174689. //www.ncbi.nlm.nih.gov/pmc/articles/PMC3234252/.

UpToDate Contents

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1. BおよびTリンパ球の正常な発生 normal b and t lymphocyte development
2. 前駆B細胞性急性リンパ芽球性白血病／リンパ腫の臨床症状、病理学的特徴、および診断 clinical manifestations pathologic features and diagnosis of precursor b cell acute lymphoblastic leukemia lymphoma
3. 重度複合型免疫不全（SCID）：特定の欠損 severe combined immunodeficiency scid specific defects
4. 原発不明の低分化癌 poorly differentiated cancer from an unknown primary site
5. 急性リンパ芽球性白血病における微小残存病変の検出 detection of minimal residual disease in acute lymphoblastic leukemia

English Journal

Adipose tissue-derived stem cells embedded with eNOS restore cardiac function in acute myocardial infarction model.

Shi CZ, Zhang XP, Lv ZW, Zhang HL, Xu JZ, Yin ZF, Yan YQ, Wang CQ.SourceDepartment of Cardiology, the Ninth Hospital Affiliated to Medical College, Shanghai Jiaotong University, ShangHai, China.
International journal of cardiology.Int J Cardiol.2012 Jan 12;154(1):2-8.
This study assessed the potential therapeutic efficacy of endothelial NO syntheses (eNOS)-expressing adipose tissue-derived stem cells (ADSCs) on infarcted hearts. We isolated CD29+, CD44+, CD45- cells from adipose tissue. Multipotent property of ADSCs was characterized by induction to differentiate
PMID 21640405

Solid-state capture and real-time analysis of individual T cell activation via self-assembly of binding multimeric proteins on functionalized materials surfaces.

Diener KR, Christo SN, Griesser SS, Sarvestani GT, Vasilev K, Griesser HJ, Hayball JD.SourceHanson Institute, Adelaide, SA 5000, Australia; School of Paediatrics and Reproductive Health, University of Adelaide, Adelaide, SA 5005, Australia.
Acta biomaterialia.Acta Biomater.2012 Jan;8(1):99-107. Epub 2011 Sep 6.
Polyfunctional T cell responses are increasingly underpinning new and improved vaccination regimens. Studies of the nature and extent of these T cell responses may be facilitated if specific T cell populations can be assessed from mixed populations by ligand-mediated capture in a solid-state assay f
PMID 21945827

Neutrophil phenotypic characteristics in children with congenital asplenia and splenectomized for hereditary spherocytosis.

Mikoluc B, Michalkiewicz J, Motkowski R, Smolka D, Pietrucha B, Piotrowska-Jastrzebska J, Bernatowska E.SourceDepartment of Pediatrics and Developmental Disorders of Children and Adolescents Medical University of Bialystok, Waszyngtona str 17 , 15-224 Bialystok , Poland.
Immunological investigations.Immunol Invest.2012;41(1):61-74. Epub 2011 Aug 30.
The spleen plays an important role in the granulocyte homeostasis due to such mechanisms as pooling, elimination of senescent cells and regulatory effects on granulocyte renewal in the bone marrow. The expression profile of granulocyte receptors was tested in children with congenital asplenia, and s
PMID 21877936

Japanese Journal

Frequency of CD45RO+ subset in CD4+CD25high regulatory T cells associated with progression of hepatocellular carcinoma

Takata Yoshiko,Nakamoto Yasunari,Nakada Akiko,Terashima Takeshi,Arihara Fumitaka,Kitahara Masaaki,Kakinoki Kaheita,Arai Kuniaki,Yamashita Taro,Sakai Yoshio,Yamashita Tatsuya,Mizukoshi Eishiro,Kaneko Shuichi
Cancer Letters 307(2), 165-173, 2011-08-28
… In HCC patients, the prevalence of CD45RO+ cells in CD4+CD25high T cells was increased and associated with higher frequencies of plasmacytoid DCs. … These results suggest that increased frequencies of the CD45RO+ subset in CD4+CD25high Tregs in HCC patients may establish the immunosuppressive environment cooperatively with tolerogenic plasmacytoid DCs to promote disease progression of liver cancer. …
NAID 120003141809

Involvement of bone-marrow-derived cells in kidney fibrosis

Wada Takashi,Sakai Norihiko,Sakai Yoshio,Matsushima Kouji,Kaneko Shuichi,Furuichi Kengo
Clinical and Experimental Nephrology 15(1), 8-13, 2011-02
… Bone-marrow-derived cells positive for CD45 or CD34, and type 1 (pro)collagen dependent on the chemokine and renin-angiotensin systems migrate into diseased kidneys and enhance synthesis matrix protein, cytokines/chemokines, and profibrotic growth factors, which may promote and escalate chronic inflammatory processes and possible interaction with resident stromal cells, thereby perpetuating kidney fibrosis. …
NAID 120002851394

Identification of a yolk sac cell population with hematopoietic activity in view of CD45/c-Kit expression

Yamasaki Shoutarou,Nobuhisa Ikuo,Ramadan Ahmed [他]
Development, growth & differentiation 53(7), 870-877, 2011-09
NAID 40019016840

Related Pictures

★リンクテーブル★

リンク元	「悪性リンパ腫」「表面抗原分類」「LCA」「記憶T細胞」
拡張検索	「CD45RO」「CD45RA」「CD45R」「CD45欠損症」
関連記事	「CD」「CD4」

「悪性リンパ腫」

Protein tyrosine phosphatase, receptor type, C
	; PDB rendering based on 1ygr.
Available structures
PDB	Ortholog search: PDBe, RCSB
List of PDB id codes
	1YGR, 1YGU
Identifiers
Symbols	PTPRC; B220; CD45; CD45R; GP180; L-CA; LCA; LY5; T200
External IDs	OMIM: 151460 MGI: 97810 HomoloGene: 2126 ChEMBL: 3243 GeneCards: PTPRC Gene
EC number	3.1.3.48
Gene Ontology
Molecular function	• protein tyrosine phosphatase activity; • transmembrane receptor protein tyrosine phosphatase activity; • protein binding; • heparin binding; • protein kinase binding; • heparan sulfate proteoglycan binding;
Cellular component	• plasma membrane; • integral to plasma membrane; • focal adhesion; • external side of plasma membrane; • membrane raft;
Biological process	• activation of MAPK activity; • negative regulation of T cell mediated cytotoxicity; • positive regulation of T cell mediated cytotoxicity; • negative regulation of cytokine-mediated signaling pathway; • hematopoietic progenitor cell differentiation; • immunoglobulin biosynthetic process; • positive regulation of humoral immune response mediated by circulating immunoglobulin; • negative regulation of protein kinase activity; • protein dephosphorylation; • negative regulation of cell adhesion involved in substrate-bound cell migration; • leukocyte cell-cell adhesion; • cell surface receptor signaling pathway; • axon guidance; • response to gamma radiation; • dephosphorylation; • B cell differentiation; • T cell differentiation; • positive regulation of B cell proliferation; • negative regulation of protein autophosphorylation; • regulation of S phase; • heterotypic cell-cell adhesion; • peptidyl-tyrosine dephosphorylation; • T cell proliferation; • B cell proliferation; • positive regulation of T cell proliferation; • positive regulation of apoptotic process; • positive thymic T cell selection; • negative thymic T cell selection; • regulation of B cell differentiation; • positive regulation of gamma-delta T cell differentiation; • positive regulation of protein kinase activity; • positive regulation of alpha-beta T cell proliferation; • positive regulation of isotype switching to IgG isotypes; • bone marrow development; • stem cell development; • negative regulation of peptidyl-tyrosine phosphorylation; • T cell receptor signaling pathway; • B cell receptor signaling pathway; • regulation of B cell receptor signaling pathway; • positive regulation of antigen receptor-mediated signaling pathway; • release of sequestered calcium ion into cytosol; • defense response to virus; • regulation of cell cycle; • positive regulation of hematopoietic stem cell migration; • positive regulation of stem cell proliferation;
	Sources: Amigo / QuickGO
RNA expression pattern
	More reference expression data
Orthologs
	This box: view; talk; edit;

　　[★]

英: malignant lymphoma
ラ: lymphoma malignum
関

悪性リンパ腫とマーカー

悪性リンパ腫.xls

sIg

CD5

bcl

TdT

その他

転座

小リンパ性リンパ腫 small lymphocytic lymphoma
慢性リンパ性白血病 chronic lymphocytic leukemia

＋

＋

＋

－

濾胞性リンパ腫 FL
　

＋

－

＋

bcl2　＋

－

MALTリンパ腫
　

－

＋

マントル細胞リンパ腫 MCL
　

＋

－

＋

＋

びまん性大細胞性B細胞リンパ腫 DLBL
　

＋

－

＋／－

＋

bcl6　＋

前駆Bリンパ芽球性リンパ腫
急性Bリンパ球性白血病 LBL/ALL

－

＋

バーキットリンパ腫 BL
　

＋

－

＋

＋

＋

Myc, Ki-67

ｔ（8,14)Myc；IgH　～80%
t(2,8)κ；Myc　～15%

ホジキンリンパ腫
　

CD15, CD30, CD45 -

t(8,22)Myc；λ　～10%

成人T細胞白血病 ATL
　

CD2, CD3, CD4, CD25, HLA-DR, CD8 -

病期

Ann Arbor分類

参考

1.

http://www.rinpashu.com/inspection/

国試

100D031

「表面抗原分類」

　　[★]

英: cluster of differentiation, CD

細胞の表面抗原を認識する抗体を整理した分類

Bリンパ球 CD10,CD19,CD20

Tリンパ球 CD2,CD3,CD5,CD7

幹細胞 CD34

顆粒球 CD13,CD33

単球 CD14：LPSをリガンドとし、Toll-like receptorと共役して細胞内シグナルを伝達する分子。

巨核球 CD41(GpIIb),CD42(GpIb)

NK細胞：CD16(IgGのFc部に対する受容体)、CD56(NCAM-I)

CD1	CD21	CD41	CD61	CD81
CD2	CD22	CD42	CD62	CD82
CD3	CD23	CD43	CD63	CD83
CD4	CD24	CD44	CD64	CD84
CD5	CD25	CD45	CD65	CD85
CD6	CD26	CD46	CD66	CD86
CD7	CD27	CD47	CD67	CD87
CD8	CD28	CD48	CD68	CD88
CD9	CD29	CD49	CD69	CD89
CD10	CD30	CD50	CD70	CD90
CD11	CD31	CD51	CD71	CD91
CD12	CD32	CD52	CD72	CD92
CD13	CD33	CD53	CD73	CD93
CD14	CD34	CD54	CD74	CD94
CD15	CD35	CD55	CD75	CD95
CD16	CD36	CD56	CD76	CD96
CD17	CD37	CD57	CD77	CD97
CD18	CD38	CD58	CD78	CD98
CD19	CD39	CD59	CD79	CD99
CD20	CD40	CD60	CD80	CD100