期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 282, 期 40, 页码 29712-29720出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M703159200
关键词
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Compared with kinases, the role of protein phosphatases in regulating biological functions is less well understood. Here we show that alpha 4, a non-catalytic subunit of the protein phosphatase 2A, plays a major role in the control of cell spreading, migration, and cytoskeletal architecture. Fibroblasts lacking alpha 4 were impaired in their ability to spread and migrate compared with wild-type cells, whereas enforced expression of alpha 4 promoted cell spreading and migration. These effects were not restricted to fibroblasts. Using a T cell-specific alpha 4 transgenic mouse model, increased alpha 4 expression was found to increase lymphocyte motility and chemotaxis. Elevated alpha 4 expression results in an increase in the GTP-bound state of Rac1, and GTP-bound Rac1 was dramatically reduced in alpha 4-deficient cells. A constitutively active mutant of Rac1 rescued the defects of cell spreading and migration caused by alpha 4 deletion, while inhibition of Rac1 blocked the ability of alpha 4 to promote cell migration. Together, these data define a novel role for the protein phosphatase 2A regulatory subunit alpha 4 in the regulation of cell spreading and migration.
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