Adenosine Deaminase-related Growth Factors (ADGFs) stimulate cell proliferation by depleting extracellular adenosine. M. Zurovec 1,2, E. Pavlova 1,2, M. Gazi 1,2, T. Dolezal 1,2, P.J. Bryant 2. 1) Physiology, Institute of Entomology, Ceske Budejovic, Czech Republic; 2) Developmental Biology Center, University of California, Irvine, Irvine, CA, 92697.
We have identified a family of six genes encoding Adenosine Deaminase-related Growth Factors (ADGFs), and carried out functional studies on these proteins in vitro. The most abundant of the proteins, ADGF-A and ADGF-D, cause serum-independent proliferation of Drosophila imaginal disc and embryonic cells in vitro. We showed that both of these proteins are active adenosine deaminase enzymes , whereas the Drosophila ortholog of authentic Adenosine Deaminase is not mitogenic and is catalytically inactive. Site-directed mutagenesis was used to show that the enzymatic activity of ADGFs is required for their mitogenic function, suggesting that the ADGFs might act simply by depleting extracellular adenosine. In support of this hypothesis, we showed that proliferation can be stimulated using bovine adenosine deaminase, or by removing sources of adenosine from the culture medium, and that proliferation is inhibited by adding adenosine to the medium. ADGFs are expressed abundantly in various tissues in vivo, suggesting that extracellular adenosine might be an important negative regulator of Drosophila cell growth.