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Protein tyrosine phosphatase, receptor type, C also known as PTPRC is an enzyme which in humans is encoded by the PTPRC gene.[1] PTPRC is also known as CD45
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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 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 which 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 pathology to differentiate between histological sections from lymphomas and carcinomas.
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. This three exons generate the RA, RB and RC isoforms.
Various isoforms of CD45 exist: CD45RA, CD45RB, CD45RC, CD45RAB, CD45RAC, CD45RBC, CD45RO, CD45R (ABC). CD45RA is located on naive T cells and CD45RO 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, CD45RO, 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,[3] Lck,[4][5] SKAP1[6] and GANAB.[7][8][9]
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. PMID 2169617. PMC 54670. 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.
- ^ Brown, V K; Ogle E W, Burkhardt A L, Rowley R B, Bolen J B, Justement L B (Jun. 1994). "Multiple components of the B cell antigen receptor complex associate with the protein tyrosine phosphatase, CD45". J. Biol. Chem. (UNITED STATES) 269 (25): 17238–44. ISSN 0021-9258. PMID 7516335.
- ^ Koretzky, G A; Kohmetscher M, Ross S (Apr. 1993). "CD45-associated kinase activity requires lck but not T cell receptor expression in the Jurkat T cell line". J. Biol. Chem. (UNITED STATES) 268 (12): 8958–64. ISSN 0021-9258. PMID 8473339.
- ^ Ng, D H; Watts J D, Aebersold R, Johnson P (Jan. 1996). "Demonstration of a direct interaction between p56lck and the cytoplasmic domain of CD45 in vitro". J. Biol. Chem. (UNITED STATES) 271 (3): 1295–300. ISSN 0021-9258. PMID 8576115.
- ^ Wu, Liangtang; Fu Jun, Shen Shi-Hsiang (Apr. 2002). "SKAP55 coupled with CD45 positively regulates T-cell receptor-mediated gene transcription". Mol. Cell. Biol. (United States) 22 (8): 2673–86. ISSN 0270-7306. PMID 11909961.
- ^ Arendt, C W; Ostergaard H L (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. (UNITED STATES) 272 (20): 13117–25. ISSN 0021-9258. PMID 9148925.
- ^ Baldwin, T A; Gogela-Spehar M, Ostergaard H L (Oct. 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. (UNITED STATES) 275 (41): 32071–6. doi:. ISSN 0021-9258. PMID 10921916.
- ^ Baldwin, T A; Ostergaard H L (Oct. 2001). "Developmentally regulated changes in glucosidase II association with, and carbohydrate content of, the protein tyrosine phosphatase CD45". J. Immunol. (United States) 167 (7): 3829–35. ISSN 0022-1767. PMID 11564800.
Further reading
- Tchilian EZ, Beverley PC (2002). "CD45 in memory and disease.". Arch. Immunol. Ther. Exp. (Warsz.) 50 (2): 85–93. PMID 12022705.
- Ishikawa H, Tsuyama N, Abroun S, et al. (2004). "Interleukin-6, CD45 and the src-kinases in myeloma cell proliferation.". Leuk. Lymphoma 44 (9): 1477–81. PMID 14565647.
- Stanton T, Boxall S, Bennett A, et al. (2004). "CD45 variant alleles: possibly increased frequency of a novel exon 4 CD45 polymorphism in HIV seropositive Ugandans.". Immunogenetics 56 (2): 107–10. doi:. PMID 15057492.
- Huntington ND, Tarlinton DM (2005). "CD45: direct and indirect government of immune regulation.". Immunol. Lett. 94 (3): 167–74. doi:. PMID 15275963.
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