ADGFs - growth factors with enzymatic activity. M. Zurovec ^1,2, T. Dolezal ^1,2, M. Gazi ^1,2, P. Bryant ¹. 1) Developmental Biology Center, University of California, Irvine, Irvine, CA 92697; 2) Institute of Entomology and University of South Bohemia, Branisovska 31,Ceske Budejovice 37005, Czech Republic.

   We have identified a novel family of polypeptide growth factors in Drosophila, which are homologous to a mitogenic growth factor recently discovered in conditioned medium from Sarcophaga cells (Homma et al. 1996). These proteins are unrelated either to known mammalian growth factors or to the previously described Imaginal Disc Growth Factors (Kawamura et al. 1998) but instead they show sequence similarity to the enzyme adenosine deaminase (ADA). We therefore refer to them as Adenosine Deaminase-Related Growth Factors or ADGFs. There are six members of ADGF family in Drosophila, and closely related proteins have been identified in moths, mollusks, vertebrates, and the slime mold Dictyostelium. A human family member has been implicated in the genetic disease Cat-Eye Syndrome. Our results show that Drosophila ADGFs differ from each other in their patterns of expression, with ADGF-A being expressed at all tested stages from embryo to adult and other ADGFs being expressed at lower levels, more abundantly in males than in females. We have produced recombinant ADGF-A and ADGF-D and shown that they are active adenosine deaminases. In the presence of insulin they cause morphological changes and serum-independent growth of several Drosophila cell types in vitro. We are testing the possibility that they function by modulating the level of extracellular adenosine.