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| Subject Categories: Signal Transduction | RNA |
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| The EMBO Journal
(2008) 27, 715–726, doi:10.1038/emboj.2008.19 Published online 14 February 2008 |
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| Regulation of stress granule dynamics by Grb7 and FAK signalling pathway |
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| Nien-Pei Tsai, Ping-Chih Ho and Li-Na Wei |
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Department of Pharmacology, University of Minnesota Medical School, Minneapolis, MN, USA To whom correspondence should be addressed Li-Na Wei, Department of Pharmacology, University of Minnesota Medical School, 6-120 Jackson Hall, 321 Church St SE, Minneapolis, MN 55455, USA. Tel.: +1 612 6259402; Fax: +1 612 6258408; E-mail: weixx009@umn.edu Received 16 October 2007; Accepted 18 January 2008; Published online 14 February 2008. |
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| Abstract |
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| Cells form stress granules (SGs) in response to environmental stresses, which constitute cytoplasmic domains where mRNAs are stored and translation is halted. Although several components are found in SGs, it is poorly understood as to how SGs are formed and dissolved. We identified growth factor receptor-bound protein 7 (Grb7), an RNA-binding, translational regulator, as an integral component of SGs, which directly interacts with Hu antigen R (HuR) and is required for cells to form SGs. When stress is terminated, Grb7 is hyperphosphorylated by focal adhesion kinase (FAK), loses its ability to directly interact with HuR and is dissociated from SG components, thereby disrupting SGs in recovering cells. Consistently, dominant-negative hypophospho mutants of FAK and Grb7 significantly attenuate SG disassembly during recovery. FAK activation followed by its phosphorylating Grb7 constitutes a cell-autonomous signalling pathway that regulates the disassembly of SGs and translational stimulation during recovery. This is the first reported pathway actively regulating the dynamics of SGs. |
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| Keywords: FAK, Grb7, stress granules |
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