The CD45 phosphotyrosine phosphatase (previously known as the leucocyte common antigen, LCA) is expressed on all nucleated haematopoietic cells and plays an important role in regulating receptor signalling thresholds in several types of immune cell. The molecule comprises a large heavily glycosylated ectodomain (391-552 amino acids) and an extensive cytoplasmic tail (700 amino acids) containing homologous domains 1 and 2 (Fig. 1). Domain 1 contains the protein tyrosine phosphatase (PTPase) activity, whereas the role of domain 2 appears to be largely regulatory. Alternative splicing generates eight or more isoforms that differ markedly in their ectodomain structures and glycosylation profiles.
An extensive range of reviews on CD45 is available (Thomas 1989; Trowbridge and Thomas 1994; Alexander 1997; Ashwell and Doro 1999; Thomas and Brown 1999; Alexander 2000; Justement 2001; Alexander 2003; Hermiston et al. 2003). This chapter will focus on the biological validation of CD45 as a pharmaceutical target and on the various approaches that have been used to inhibit CD45 activity and function.
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