RRC ID 44254
Author Iwasaki T, Katayama T, Kohama K, Endo Y, Sawasaki T.
Title Myosin phosphatase is inactivated by caspase-3 cleavage and phosphorylation of myosin phosphatase targeting subunit 1 during apoptosis.
Journal Mol Biol Cell
Abstract In nonapoptotic cells, the phosphorylation level of myosin II is constantly maintained by myosin kinases and myosin phosphatase. During apoptosis, caspase-3-activated Rho-associated protein kinase I triggers hyperphosphorylation of myosin II, leading to membrane blebbing. Although inhibition of myosin phosphatase could also contribute to myosin II phosphorylation, little is known about the regulation of myosin phosphatase in apoptosis. In this study, we have demonstrated that, in apoptotic cells, the myosin-binding domain of myosin phosphatase targeting subunit 1 (MYPT1) is cleaved by caspase-3 at Asp-884, and the cleaved MYPT1 is strongly phosphorylated at Thr-696 and Thr-853, phosphorylation of which is known to inhibit myosin II binding. Expression of the caspase-3 cleaved form of MYPT1 that lacked the C-terminal end in HeLa cells caused the dissociation of MYPT1 from actin stress fibers. The dephosphorylation activity of myosin phosphatase immunoprecipitated from the apoptotic cells was lower than that from the nonapoptotic control cells. These results suggest that down-regulation of MYPT1 may play a role in promoting hyperphosphorylation of myosin II by inhibiting the dephosphorylation of myosin II during apoptosis.
Volume 24(6)
Pages 748-56
Published 2013-3-1
DOI 10.1091/mbc.E11-08-0740
PII mbc.E11-08-0740
PMID 23345589
PMC PMC3596246
MeSH Amino Acid Sequence Apoptosis* Caspase 3 / metabolism* Cell Line, Tumor Cell Membrane / ultrastructure Down-Regulation HeLa Cells Humans Myosin Type II / metabolism* Myosin-Light-Chain Phosphatase / genetics Myosin-Light-Chain Phosphatase / metabolism* Phosphorylation Protein Binding RNA Interference RNA, Small Interfering Sequence Analysis, Protein rho-Associated Kinases / metabolism
IF 3.905
Times Cited 10
WOS Category CELL BIOLOGY
Resource
Human and Animal Cells