1. Departments of Biological Chemistry and
2. Dermatology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA

Correspondence to: Pierre A. Coulombe^1,2 Correspondence and requests for materials should be addressed to P.A.C. (Email: coulombe@jhmi.edu).

Abstract

Cell growth, an increase in mass and size, is a highly regulated cellular event. The Akt/mTOR (mammalian target of rapamycin) signalling pathway has a central role in the control of protein synthesis and thus the growth of cells, tissues and organisms¹. A striking example of a physiological context requiring rapid cell growth is tissue repair in response to injury². Here we show that keratin 17, an intermediate filament protein rapidly induced in wounded stratified epithelia³, regulates cell growth through binding to the adaptor protein 14-3-3. Mouse skin keratinocytes lacking keratin 17 (ref. 4) show depressed protein translation and are of smaller size, correlating with decreased Akt/mTOR signalling activity. Other signalling kinases have normal activity, pointing to the specificity of this defect. Two amino acid residues located in the amino-terminal head domain of keratin 17 are required for the serum-dependent relocalization of 14-3-3 from the nucleus to the cytoplasm, and for the concomitant stimulation of mTOR activity and cell growth. These findings reveal a new and unexpected role for the intermediate filament cytoskeleton in influencing cell growth and size by regulating protein synthesis.

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