Adenosine Deaminase-Related Growth Factors

University Of California-Irvine, Irvine CA

Investigators

Abstract

0091348 Bryant This project concerns a novel family of polypeptide growth factors (Adenosine Deaminase-related Growth Factors or ADGFs) recently discovered as a component of conditioned medium from insect cells, and as products of the larval salivary gland in several insects. They show strong sequence similarity to the enzyme Adenosine Deaminase and are predicted to be secreted, but have several alterations leading to the prediction that they may not be deaminases but have a different catalytic or non-catalytic function. A human family member has been implicated in the genetic disease Cat-Eye Syndrome. We have identified five members of the family in Drosophila by genomic and cDNA sequence analysis, and shown that one of them, ADGF-A, which is strongly expressed in the embryonic mesoderm, promotes progression through the S phase of the cell cycle in imaginal disc cells. ADGF-A is expressed throughout development, and data in the literature suggest that the main source may be the salivary gland. Other family members are also expressed at most developmental stages, but more weakly than ADGF-A. We will complete our analysis of the expression patterns of these genes in vivo, test whether their expression is regulated by nutrition, and determine whether any Drosophila cell lines produce ADGFs during medium conditioning. The mode of action of the ADGFs will be investigated using cultured imaginal disc cells, including tests for binding to candidate cell-surface receptors, identification of the signal transduction pathways that are activated, and an investigation of how cell-cycle parameters are controlled by these and other growth factors. The possible catalytic activity of these proteins on adenosine will be tested biochemically, and a collaborative study will be launched to analyze the three-dimensional structure of ADGF-A. The project will contribute to our basic understanding of growth regulation, and to the underlying mechanisms leading to human genetic disease.