By Sean Henahan, Access Excellence

REHOVOT, Israel- Regulatory proteins involved in the growth and development of fly and possibly mammalian embryos, are controlled by warring signals that keep each other in check in a way that is now only being understood, according to a Weizmann Institute study.

The scientists studied a protein called Argos in Drosophila, the fruit fly. Drosophila is commonly used in genetic research because it reproduces quickly and contains several key proteins homologous to those in mammals, including man. Argos regulates the development of eye, wing and other tissues in the fly, and the researchers have now determined how it does so.

Prof. Ben-Zion Shilo and doctoral student Ronen Schweitzer of the Weizmann Institute, collaborating with a team headed by Dr. Matthew Freeman of the Medical Research Council in Cambridge, England, showed in vivo that Argos blocks the pathway of a growth hormone receptor called DER, which is involved in many stages of fly development, including the formation of photoreceptors in the eye and veins in the wing.

They also demonstrated in vitro that Argos is able to repress DER activity by neutralizing the effect of Spitz, the protein that activates DER. Thus cell development is regulated by a balance of opposing signals -- Argos, on the one hand, and Spitz, on the other. This is the first in vivo demonstration that growth hormone receptors are inhibited by factors outside, rather than inside, the cell.

"This raises the possibility that a mammalian homologue of Argos may exist, and it will be interesting to see whether similar extracellular inhibition of growth hormone receptors occurs in vertebrates. The possibility of engineering Argos-like inhibitors in mammals may be of theoretical and clinical interest," notes Prof. Shilo, who is Head of the Weizmann Institute's Department of Genetics and Virology.

The mammalian versions of DER and Spitz are known to be involved in the proliferation not only of normal cells, but of malignant ones as well. The discovery of this previously unknown mechanism may some day lead to new approaches for the regulation of cell division. If opposing chemical signals that compete over the same receptor do exist in man, this could lead to new approaches for treating insufficient or excess cell growth, characteristic of many developmental, immune system, and malignant diseases, he said.

This study appeared in Nature, 8/24/95, Vol. 376, pp. 699-702.