Protein tyrosine phosphatase receptor type C (PTPRC or CD45)

Abstract

The leucocyte common antigen, protein tyrosine phosphatase receptor type C (PTPRC), also known as CD45, is a transmembrane glycoprotein, expressed on almost all haematopoietic cells except for mature erythrocytes, and is an essential regulator of T and B cell antigen receptor-mediated activation. Disruption of the equilibrium between protein tyrosine kinase and phosphatase activity (from CD45 and others) can result in immunodeficiency, autoimmunity, or malignancy. CD45 is normally present on the cell surface, therefore it works upstream of a large signalling network which differs between cell types, and thus the effects of CD45 on these cells are also different. However, it is becoming clear that CD45 plays an essential role in the innate immune system and this is likely to be a key area for future research. In this review of PTPRC (CD45), its structure and biological activities as well as abnormal expression of CD45 in leukaemia and lymphoma will be discussed.

Keywords: hematology; leukemia; myeloid; myeloproliferative disorders.

Figure 1

An illustration of CD45 structure. Different types of CD45 isoforms are expressed by haematopoietic stem cells (HSCs) based on alternative splicing of exons A, B and C. This results in modifications of the NH2-terminal domain of approximately 200 amino acids that contains many residues such as serine and threonine. This portion of CD45 structure is rich of O-glycosylation events which explains the distinctive glycosylation patterns of each CD45 isoform. Consequently, different lineages of HSCs express different types of CD45 isoforms based on different stages of differentiation and glycosylation events. The cysteine rich domain is connected by three fibronectin type III (FN III-like) repeats, a transmembrane domain followed by a cytoplasmic tail which contains two protein tyrosine phosphatase (PTPase) regions (D1 and D2). While D1 is characterised by PTPase activity, D2 has no enzymatic activity, but it is necessary for CD45 substrate recruitment and provide flexibility in folding of the molecule.

Figure 2

CD45 isoform expression on human erythroid, lymphoid and myeloid haemopoietic cells at various stages of differentiation. RA, expressed on naïve T cells, has exon four with deficiency in exon 5 and 6. RB has only exon 5, expressed mainly on B cells, naïve T cells and thymocytes. RBC, has exons 5 and 6 of the CD45 gene. RABC, has all of the three exons 4, 6, and 6. RO, expressed on granulocytes, activated and memory T cells, some B subsets and activated monocytes/macrophages, has exon 3, 7 and 8 with deficiency in RA, RB and RC exons of the CD45 gene. ‘+’ means brighter expression (modified from Craig et al). NK, natural killer.

Figure 3

CD45 gene polymorphism and disease consequences. C77G and A138G are the two CD45 polymorphisms affecting PTPRC gene in human. While C77G target exon four splice silencer which affects the expression of CD45RO and leads to immune disorders such as multiple sclerosis and HIV infection, A138G polymorphism is a substitution of exon six and results in high expression of CD45RO with subsequent immune disorders such as hepatitis B infection and Grave’s disease.