|Protein tyrosine phosphatase, receptor type, C|
PDB rendering based on 1ygr.
|Symbols||; LCA; B220; CD45; GP180; LY5; T200|
|External IDs||Template:OMIM5 Template:MGI|
|RNA expression pattern|
|Template:GNF Ortholog box|
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.
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).
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). 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 Syk (in B cells) and activates it.
- 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:10.1007/s00251-004-0668-z. PMID 15057492.
- Huntington ND, Tarlinton DM (2005). "CD45: direct and indirect government of immune regulation". Immunol. Lett. 94 (3): 167–74. doi:10.1016/j.imlet.2004.05.011. PMID 15275963.
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