The PP2A-associated Protein α4 Plays a Critical Role in the Regulation of Cell Spreading and Migration

Mei Kong, Thi V. Bui, Dara Ditsworth, Josh J. Gruber, Dmitry Goncharov, Vera P. Krymskaya, Tullia Lindsten, Craig B. Thompson
2007 Journal of Biological Chemistry  
Compared with kinases, the role of protein phosphatases in regulating biological functions is less well understood. Here we show that ␣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 ␣4 were impaired in their ability to spread and migrate compared with wild-type cells, whereas enforced expression of ␣4 promoted cell spreading and migration. These effects were not
more » ... d to fibroblasts. Using a T cell-specific ␣4 transgenic mouse model, increased ␣4 expression was found to increase lymphocyte motility and chemotaxis. Elevated ␣4 expression results in an increase in the GTP-bound state of Rac1, and GTP-bound Rac1 was dramatically reduced in ␣4-deficient cells. A constitutively active mutant of Rac1 rescued the defects of cell spreading and migration caused by ␣4 deletion, while inhibition of Rac1 blocked the ability of ␣4 to promote cell migration. Together, these data define a novel role for the protein phosphatase 2A regulatory subunit ␣4 in the regulation of cell spreading and migration. . 3 The abbreviations used are: PP2A, protein phosphatase 2A; MEF, mouse embryonic fibroblast; DMEM, Dulbecco's modified Eagle's medium; FBS, fetal bovine serum; FN, fibronectin; SDF, stromal cell-derived factor; FITC, fluorescein isothiocyanate; GFP, green fluorescence protein; TOR, target of rapamycin; ER, estrogen receptor. 4 M. Kong, unpublished data.
doi:10.1074/jbc.m703159200 pmid:17693407 fatcat:uwxxygspu5eqbcbnhs7aabjxfm