Ecto‐phosphodiesterase/pyrophosphatase of lymphocytes and non‐lymphoid cells: structure and function of the PC‐1 family

Immunological Reviews - Tập 161 Số 1 - Trang 11-26 - 1998
James W. Goding1, Robert Terkeltaub2, Michèle Maurice3, Philippe Déterre4, A. Sali1, Sabina I. Belli5
1Department of Pathology and Immunology, Monash Medical School, Alfred Hospital, Prahran, Victoria, Australia
2Veterans Affairs Medical Center San Diego, La Jolla, California, USA.
3INSERM, CJF 96-07, Faculté de médecine Saint Antoine, Paris, France
4Laboratoire d'lmmunologie Cellulaire, Groupe Hospitalier Pitie‐Salpetriere Bat. CERVI, Paris, France.
5Institut de Biochimie, Epalinges, Switzerland.

Tóm tắt

Summary: Many developmentally regulated membrane proteins of lymphocytes are ecto‐enzymes, with their active sites on the external surface of the cell. These enzymes commonly have peptidase, phosphodiesterase or nucleotidase activity. Their biological roles are just beginning to be discovered. Although their expression is usually associated with particular stages of lymphoid differentiation, the same gene products are often expressed on the surface of certain non‐lymphoid cell types outside the immune system, indicating that their functions cannot be unique to lymphocytes, nor can they be ubiquitous. The plasma cell membrane protein PC‐1 (phosphodiesterase I; EC 3.1.4.1/nucleotide pyrophosphatase; EC 3.6.1.9), which was one of the first serological markers for lymphocyte subsets to be discovered, is a typical example. Within the immune system, PC‐1 is confined to plasma cells, which represent about 0.1% of lymphocytes. However, PC‐1 is also expressed on cells of the distal convoluted tubule of the kidney, chondrocytes, osteoblasts, epididymis and hepatocytes. Recent work has shown that PC‐1 is a member of a multigene family of ecto‐phosphodiesterases that currently has two other members, PD‐1α (autotaxin) and PD‐1β (B10). Within this family, the extracellular domains are highly conserved, especially around the active site. In contrast, the transmembrane and cytopiasmic domains are highly divergent. Individual members of the ecto‐phosphodiesterase family have distinct patterns of distribution in different cell types, and even within the same cell. For example, PC‐1 is present only on the basolateral surface of hepatocytes, while B10 (PD‐1β) is confined to the apical surface. Analysis of conservation and differences in the sequence of their cytoplasmic tails may illuminate intracellular tar‐getting signals. Ecto‐phosphodiesterases may play a part in diverse activities in different tissues, including recycling of nucleotides. They may also regulate the concentration of pharmacologically active extracellular compounds such as adenosine or its derivatives and ceil motility. Some members may modulate local concentrations of pyrophosphate, and hence influence calcification in bone and cartilage.

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Immunological Reviews

Tập 161 Số 1

11-26

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