In the imaginal discs of Drosophila, contact-dependent cell interactions are important both for promoting cell proliferation and for limiting it at the end of the growth period. However, recent work indicates that diffusible growth factors are also important in regulating growth and proliferation. We have identified a family of five imaginal disc growth factors (IDGFs) by purifying mitogenic proteins that accumulate in conditioned medium during culture of imaginal disc cell lines. These proteins cooperate with insulin to stimulate not only proliferation, but also polarization and motility of imaginal disc cells. They are produced by the fat body and are probably active on a variety of peripheral tissues. The IDGFs are structurally related to chitinases, but they show an amino acid substitution that is known to abrogate catalytic activity and to transform chitinases into lectins. We suggest that these proteins act as endogenous mitogenic lectins and mediate nutritional effects on tissue growth, possibly by interacting with the insulin receptor pathway. Glycoproteins similar to the IDGFs are found in mammals and may constitute a novel class of growth factors and/or inflammatory cytokines.
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