Mollusk-Derived Growth Factor and the New Subfamily of Adenosine Deaminase-related Growth Factors

Peptide and protein growth factors play critical roles in the control of proliferation, differentiation and survival of most, if not all, cell types. In this review, we describe a newly isolated growth factor from Aplysia californica, mollusk derived growth factor (MDGF), that is a member of the adenosine deaminase-related growth factor (ADGF) subfamily. Other known subfamily members from a range of invertebrate and vertebrate species include: insect-derived growth factor, Drosophila ADGFs, tsetse salivary growth factors, insect adenosine deaminases (ADAs; Lutzomyia, Culex, Aedes, Anopheles), and cat eye syndrome critical region gene 1 (CECR1) in humans, pigs, and zebrafish. ADGFs from vertebrates and invertebrates contain both an ADA domain and a novel N-terminal region of about 100 amino acids. Catalytic residues involved in ADA activity are conserved in ADGFs, and inhibitors of ADA can block ADGF activity. ADA enzymatic activity has been shown, by inhibitor and site-directed mutagenesis studies, to be related to the ability of ADGFs from many species to stimulate cell proliferation. The available evidence suggests that the conversion of adenosine to inosine (or their analogs) is important for the mitogenic actions of ADGFs. Future investigations of this novel subfamily should lead to the identification of their receptors.