The invertebrate growth factor/CECR1 subfamily of adenosine deaminase proteins

Adenosine deaminase (ADA) catalyzes the hydrolysis of adenosine to inosine. Its lack determines severe combined immunodeficiency in mammals, possibly due to accumulation of extracellular adenosine, which induces apoptosis in lymphocytes (Franco et al., 1998). Thus, presence of normal levels of ADA l eads to normal growth and proliferation of lymphocytes. Several vertebrate and microbial ADA aminoacid sequences are known, with substantial similarit y to each other. On the other hand, there are invertebrate growth factors a s well as a candidate gene for the human cat eye syndrome (CECR1) (Riazi et al., 2000. Genomics 64, 277-285), which share substantial similarity to ea ch other, and also to ADA. In this study, we report the expression and ADA enzymatic activity of a cDNA from the salivary glands of Lutzomyia longipal pis, a blood-sucking insect, with substantial similarity to insect growth f actors and to human CECR1. We also demonstrate the existence of a subfamily of the adenosine deaminase family characterized by their unique amino-term inal region. Both Drosophila melanogaster and humans have both types of ade nosine deaminases. Results indicate that these invertebrate proteins previo usly annotated as growth factors, as well as the human CECR1 gene product, may exert their actions through adenosine depletion. The different roles pl ayed by each type of adenosine deaminase in humans and Drosophila remains t o be fully investigated. (C) 2001 Elsevier Science B.V. All rights reserved .