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Development 129, 4103-4109 (2002)
© 2002 The Company of Biologists Limited

The Drosophila insulin/IGF receptor controls growth and size by modulating PtdInsP3 levels

Sean Oldham1, Hugo Stocker1, Muriel Laffargue2, Franz Wittwer1, Matthias Wymann2 and Ernst Hafen1,*

1 Universität Zürich, Zoologisches Institut, Winterthurerstrasse 190, CH – 8057, Zürich, Switzerland
2 Université de Fribourg, Institute de Biochemie, Rue du Musée 5, CH – 1700, Fribourg, Switzerland

*Author for correspondence (e-mail: hafen{at}zool.unizh.ch)

Accepted 10 June 2002

Understanding the control of size is of fundamental biological and clinical importance. Insulin/IGF signaling during development controls growth and size, possibly by coordinating the activities of the Ras and PI 3-kinase signaling pathways. We show that in Drosophila mutating the consensus binding site for the Ras pathway adaptor Drk/Grb2 in Chico/IRS does not interfere with growth whereas mutating the binding sites of the PI 3-kinase adaptor p60 completely abrogates Chico function. Furthermore, we present biochemical and genetic evidence that loss of the homolog of the tumor suppressor gene, Pten, results in increased PtdInsP3 levels and that these increased levels are sufficient to compensate for the complete loss of the Insulin/insulin-like growth factor receptor function. This reduction of Pten activity is also sufficient to vastly increase organism size. These results suggest that PtdInsP3 is a second messenger for growth and that levels of PtdInsP3 during development regulate organismal size.

Key words: Growth, PtdInsP3, Pten, Cancer, Tumor suppressor, Insulin, PI 3 kinase




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© The Company of Biologists Ltd 2002