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Susi, a negative regulator of Drosophila PI3-kinase.


Wittwer, F; Jaquenoud, M; Brogiolo, W; Zarske, M; Wüstemann, P; Fernandez, R; Stocker, H; Wymann, M P; Hafen, E (2005). Susi, a negative regulator of Drosophila PI3-kinase. Developmental Cell, 8(6):817-827.

Abstract

The Phosphatidylinositol-3 kinase/Protein Kinase B (PI3K/PKB) signaling pathway controls growth, metabolism, and lifespan in animals, and deregulation of its activity is associated with diabetes and cancer in humans. Here, we describe Susi, a coiled-coil domain protein that acts as a negative regulator of insulin signaling in Drosophila. Whereas loss of Susi function increases body size, overexpression of Susi reduces growth. We provide genetic evidence that Susi negatively regulates dPI3K activity. Susi directly binds to dP60, the regulatory subunit of dPI3K. Since Susi has no overt similarity to known inhibitors of PI3K/PKB signaling, it defines a novel mechanism by which this signaling cascade is kept in check. The fact that Susi is expressed in a circadian rhythm, with highest levels during the night, suggests that Susi attenuates insulin signaling during the fasting period.

Abstract

The Phosphatidylinositol-3 kinase/Protein Kinase B (PI3K/PKB) signaling pathway controls growth, metabolism, and lifespan in animals, and deregulation of its activity is associated with diabetes and cancer in humans. Here, we describe Susi, a coiled-coil domain protein that acts as a negative regulator of insulin signaling in Drosophila. Whereas loss of Susi function increases body size, overexpression of Susi reduces growth. We provide genetic evidence that Susi negatively regulates dPI3K activity. Susi directly binds to dP60, the regulatory subunit of dPI3K. Since Susi has no overt similarity to known inhibitors of PI3K/PKB signaling, it defines a novel mechanism by which this signaling cascade is kept in check. The fact that Susi is expressed in a circadian rhythm, with highest levels during the night, suggests that Susi attenuates insulin signaling during the fasting period.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:07 Faculty of Science > Institute of Zoology (former)
Dewey Decimal Classification:570 Life sciences; biology
590 Animals (Zoology)
Language:English
Date:1 June 2005
Deposited On:11 Feb 2008 12:17
Last Modified:21 Nov 2017 13:22
Publisher:Elsevier
ISSN:1534-5807
Publisher DOI:https://doi.org/10.1016/j.devcel.2005.04.002
PubMed ID:15935772

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