PTPRC

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

Function
The protein encoded by this gene is a member of the is_associated_with::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.

It is a type I is_associated_with::transmembrane protein that is in various forms present on all differentiated is_associated_with::hematopoietic cells, except is_associated_with::erythrocytes and is_associated_with::plasma cells, that assists in the activation of those cells (a form of is_associated_with::co-stimulation). It is expressed in is_associated_with::lymphomas, is_associated_with::B-cell is_associated_with::chronic lymphocytic leukemia, is_associated_with::hairy cell leukemia, and is_associated_with::acute nonlymphocytic leukemia. A is_associated_with::monoclonal antibody to CD45 is used in routine is_associated_with::immunohistochemistry 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 is_associated_with::exons and three exons of the primary transcripts are alternatively spliced to generate up to eight different mature is_associated_with::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, 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 is_associated_with::tyrosine kinase called is_associated_with::Lck (in T cells) or is_associated_with::Lyn/Fyn/Lck (in B cells) and activates it.

Interactions
PTPRC has been shown to interact with:


 * is_associated_with::GANAB,
 * is_associated_with::LYN,
 * is_associated_with::Lck,  and
 * is_associated_with::SKAP1.

CD45 has been recently shown to interact with the is_associated_with::HCMV UL11 protein. This interaction results in functional paralysis of is_associated_with::T cells.

Clinical importance
Stem cells of several varieties, including is_associated_with::mesenchymal stem cells and is_associated_with::hæmatopoietic stem cells are found in the is_associated_with::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 is_associated_with::alleles of CD45 in mice: CD45.1 (Ly5.1 historically) and CD45.2 (Ly5.2 historically). 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, is_associated_with::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 use of CD90 (Thy1) alleles. The CD90.1/CD90.2 system is used in the same manner as the CD45.1/CD45.2 system.