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Bimodal expression of Sprouty2 during the cell cycle is mediated by phase-specific Ras/MAPK and c-Cbl activities

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Abstract

Sprouty2 is an important inhibitor of cell proliferation and signal transduction. In this study, we found a bimodal expression of Sprouty2 protein during cell cycle progression after exit from quiescence, whereas elevated Sprouty4 expression in the G1 phase stayed high throughout the rest of the cell cycle. Induction of the mitogen-activated protein kinase via activated Ras was crucial for increased Sprouty2 expression at the G0/G1 transition. Following the first peak, accelerated proteasomal protein degradation caused a transient attenuation of Sprouty2 abundance during late G1. Since the decline in its expression was abolished by dominant negative c-Cbl and the timely restricted interaction between Sprouty2 and c-Cbl disappeared at the second peak of Sprouty2 expression, we conclude that the second phase in the cell cycle-specific expression profile of Sprouty2 is solely dependent on ubiquitination by c-Cbl. Our results suggest that Sprouty2 abundance is the result of strictly coordinated activities of Ras and c-Cbl.

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Acknowledgments

This study was supported by Herzfelder’sche Familienstiftung 07 and the Fonds der Stadt Wien für Innovative Interdisziplinäre Krebsforschung, project number K-7/07.

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  1. Christoph-Erik Mayer

    Present address: Helmholtz Zentrum München (German Research Center for Environmental Health), Marchioninistrasse 25, 81377, Munich, Germany

Authors and Affiliations

  1. Department of Medicine I, Institute of Cancer Research, Medical University of Vienna, Borschkegasse 8a, 1090, Vienna, Austria

    Christoph-Erik Mayer, Barbara Haigl, Florian Jantscher, Gerald Siegwart, Michael Grusch, Walter Berger & Hedwig Sutterlüty

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Correspondence to Hedwig Sutterlüty.

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Mayer, CE., Haigl, B., Jantscher, F. et al. Bimodal expression of Sprouty2 during the cell cycle is mediated by phase-specific Ras/MAPK and c-Cbl activities. Cell. Mol. Life Sci. 67, 3299–3311 (2010). https://doi.org/10.1007/s00018-010-0379-6

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