CD45

Abstract

CD45 (also known as leukocyte common antigen (LCA), EC 3.1.3.48, T200, Ly5, PTPRC, and B220) constitutes the first and prototypic receptor-like protein tyrosine phosphatase (RPTP). This chapter briefly summarizes the current understanding of the structure, function, and regulation of this key phosphatase. CD45 belongs to a large family of type I transmembrane receptor-like protein tyrosine phosphatases (RPTPs). The large extracellular domain of CD45 is heavily glycosylated and contains three alternatively spliced exons (4, 5, and 6) that are both O-linked glycosylated and sialylated. Alternative splicing of these exons produces isoforms differing in size, shape, and charge. Studies using CD45-deficient T and B cell lines demonstrate that CD45 is an obligate positive regulator of antigen receptor signaling. Ablation of the murine CD45 gene by three independent groups reveals its critical positive role in lymphocyte development and activation. Although CD45 clearly plays a positive role in antigen receptor signaling, it can also function as a negative regulator in other settings, such as hyperphosphorylation of the negative regulatory tyrosin. The discrepancy of positive and negative effects of CD45 may be explained by its inclusion in or exclusion from clustered signaling complexes. Further research is clearly needed to fully elucidate the answers to questions regarding the physiological significance of CD45.