Bistratene A causes phosphorylation of talin and redistribution of actin microfilaments in fibroblasts: possible role for PKC-delta.
Bistratene A is a marine toxin which induces phosphorylation of cellular proteins. Our current evidence indicates that this occurs through activation of protein kinase C-delta. In fibroblasts bistratene A causes rounding up of the cells and a rapid disappearance of vinculin staining and actin stress fibers as detected by fluorescence immunohistochemistry. Phosphorylation of the focal adhesion protein, talin, is increased after bistratene A treatment and this is inhibited by calphostin C, a specific inhibitor of PKC. No changes in the phosphorylation status of vinculin, tubulin, or vimentin were observed in the presence of the toxin. Treatment with bistratene A caused a redistribution of PKC-delta from cytosolic and membrane compartments to the nuclear fraction. There was no effect on the subcellular distribution of any other PKC isoform. These results demonstrate that phosphorylation of talin is implicated in the disruption of actin microfilaments in fibroblasts by bistratene A and that this is most likely mediated by PKC-delta.
Watters
D
D
Queensland Cancer Fund Research Unit, Royal Brisbane Hospital, Herston, 4029, Australia. dianneW@qimr.edu.au
Garrone
B
B
Gobert
G
G
Williams
S
S
Gardiner
R
R
Lavin
M
M
D000081:Acetamides; D008841:Actin Cytoskeleton / Q000187:drug effects* / Q000378:metabolism; D000199:Actins / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000378:metabolism; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D004988:Ethers, Cyclic / Q000633:toxicity*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000378:metabolism*; D008387:Marine Toxins / Q000633:toxicity*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism*; D051745:Protein Kinase C-delta; D011714:Pyrans; D013141:Spiro Compounds; D016608:Talin / Q000378:metabolism*
D000081:Acetamides; D000199:Actins; D003598:Cytoskeletal Proteins; D004988:Ethers, Cyclic; D007527:Isoenzymes; D008387:Marine Toxins; D011714:Pyrans; D013141:Spiro Compounds; D016608:Talin; C059975:bistratene A; C497258:PRKCD protein, human; D011493:Protein Kinase C; D051745:Protein Kinase C-delta