The tumour suppressor RASSF1A is a novel substrate of PKC.
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.
Verma
Sunil K
SK
Department of Medical Oncology, Medical Sciences Division, The University of Oxford, Oxford, UK.
Ganesan
Trivadi S
TS
Parker
Peter J
PJ
D000595:Amino Acid Sequence; D006801:Humans; D008870:Microtubules / Q000378:metabolism* / Q000648:ultrastructure; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism*; D013379:Substrate Specificity; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
C411762:RASSF1 protein, human; D025521:Tumor Suppressor Proteins; D011493:Protein Kinase C