Verma, S. K., et al. (2008). FEBS Letters 582, 2270-2276.

The tumour suppressor RASSF1A is a novel substrate of PKC

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Sunil K. Vermaa, b, c, 1, Trivadi S. Ganesana, b, 2, Peter J. Parkerc, d

a Department of Medical Oncology, Medical Sciences Division, The University of Oxford, Oxford, UK
b Ovarian Cancer Group, CRUK Molecular Oncology Laboratories, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford OX3 9DS, UK
c Protein Phosphorylation Laboratory, London Research Institute, CRUK Lincoln’s Inn Fields Laboratories, 44 Lincoln’s Inn Fields, London WC2A 3PX, UK
d Kings College London, The Division of Cancer Studies, Section of Cancer Cell Biology and Imaging, 2nd Floor, New Hunt’s House, Guy’s Hospital, St. Thomas Street, London SE1 1UL, UK

Abstract

Ras association domain family 1A (RASSF1A) is a tumour suppressor that contains an amino-terminal cysteine-rich region, similar to the diacylglycerol (DAG)-binding domain (C1 domain) found in the protein kinase C (PKC) family of proteins, and a carboxy-terminal Ras-association (RA) domain. In the present study, RASSF1A was identified as a substrate for PKC. Using classical biochemical approaches, it was established that S197 and S203 within the RA domain of RASSF1A are phosphorylated by PKC in vitro and in vivo. Unlike the WT protein, the S197, 203D double mutant of RASSF1A failed to modulate microtubule organization and perinuclear vimentin collapse. By contrast, the equivalent AA mutant of RASSF1A phenocopied the WT protein. These findings indicate that PKC phosphorylation of RASSF1A regulates its ability to reorganize the microtubule network.

Abbreviations

RASSF1A, Ras association domain family 1A; PKC, protein kinase C; PMA, phorbol 12-myristate 13-acetate;
DAG, diacylglycerol; DAPI, 4′,6-diamidine-2′-phenylindole dihydrochloride


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Keywords

RASSF1A; Protein kinase C; Microtubule organization; Vimentin

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The tumour suppressor RASSF1A is a novel substrate of PKC

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Verma, S. K., Ganesan, T. S. and Parker, P. J. (2008). The tumour suppressor RASSF1A is a novel substrate of PKC. FEBS Letters 582, 2270-2276.

Short Citation Verma, S. K., et al. (2008). FEBS Letters 582, 2270-2276.
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