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Proteolytic cleavages give receptor tyrosine kinases the gift of ubiquity

Oncogene volume 28, pages 2185–2195 (2009)Cite this article

Abstract

Receptor tyrosine kinases (RTK) constitute a large family of membrane receptors which, in response to their respective ligand, transmit information into cells. RTK regulate multiple biological responses, and their deregulation is often associated with tumourigenesis. The intracellular signalling pathways initiated by full-length membrane RTK are studied extensively, but many RTK fragments showing unexpected cellular localization have been observed. These fragments are generated by proteolytic cleavages, catalyzed notably by caspases, membrane metalloproteases or γ-secretase. Interestingly, these cleavages, in addition to regulating membrane receptor levels, generate active fragments that can regulate biological processes, such as transcription or the survival/apoptosis balance. Thus, proteolytic cleavages release RTK from the membrane and extend their functions. Furthermore, the RTK proteolysis are involved in regulating cell transformation, which highlights their potential as attractive targets for therapeutic strategies.

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Acknowledgements

This work was supported by the CNRS, the Institut Pasteur de Lille, and INSERM, and by grants from the ‘Ligue contre le Cancer, comité Nord’, the ‘Association pour la Recherche sur le Cancer’, the ‘Fondation Recherche Médicale, Comité Nord-Pas de Calais’ and ‘Agence Nationale de la Recherche, Young Investigator Program’. BF was supported by a ‘Institut Pasteur/Région Nord-Pas de Calais’ fellowship and FA and JL by grants from the French Research and Technology Minister.

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  1. CNRS UMR 8161, Institut de Biologie de Lille-Institut Pasteur de Lille-Université de Lille 1-Université de Lille 2, Lille, France

    F Ancot, B Foveau, J Lefebvre, C Leroy & D Tulasne

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Ancot, F., Foveau, B., Lefebvre, J. et al. Proteolytic cleavages give receptor tyrosine kinases the gift of ubiquity. Oncogene 28, 2185–2195 (2009). https://doi.org/10.1038/onc.2009.88

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