Receptor-dependent protein activation without a receptor

Activation of G-Proteins was previously thought to be exclusively triggered by extracellular stimuli. Now Dr. Jrgen Knoblich and his group at the Research Institute of Molecular Pathology, Vienna (Austria), provide in vivo evidence for G-Protein activation solely by an intracellular protein.

"G-Protein activation was predominantly seen as a "relay station integrating extracellular signals via membrane spanning receptors with intracellular responses. The central role of this activation in cell responses to hormones and neurotransmitters makes G-proteins a major target for a wide range of powerful pharmaceuticals in humans. However, we now believe that a cellular mechanism exists which can activate these key proteins without extracellular stimulation. This fundamental insight could help gaining better understanding of disease mechanisms and will aid the development of novel therapies comments Dr. Knoblich.

Published in tomorrows issue of Cell (Vol. 107/2). the work by Knoblich describes a role for the cellular protein Pins (Partner of Inscuteable) in the localised activation of G-proteins in asymmetrically dividing cells of the developing Drosophila nervous system. Autonomous activation of G-proteins is shown to be part of a synchronised interaction of several proteins in differentiating neuroblasts. The receptor-independent activation of G-proteins is believed to support cellular polarity not only in neuroblasts but also in precursor cells of sensory organs (SOPs). Such establishment and maintenance of cellular polarity is essential for correct differentiation of these cells after delamination from adjacent tissue.

Previous work by Stephen Lanier and colleagues at the Medical University of South Carolina showed that Pins are conserved in humans and can activate G-proteins under controlled in vitro conditions. Taken together with the in vivo data from Drosophila reported here it is believed that receptor-independent G-protein activation plays an

Contact: Heidemarie Hurtl
PR&D Public Relations for Research & Development

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