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pubmed:abstractText |
Serine/threonine protein phosphatase (PP) 2A is thought to dephosphorylate phosphorylated beta1 integrin to link with actin filaments (F-actin). However, whether PP2A participates in the regulation of F-actin assembly to which beta1 integrin is anchored is unclear. We report here that the core enzyme of PP2A (PP2A-AC), consisting of the regulatory subunit A (PP2A-A) and the catalytic subunit C (PP2A-C), forms a complex with beta1 integrin, a small GTPase Rac, and its effector IQGAP1 in non-malignant human mammary epithelial (HME) cells. Treatment of HME cells with okadaic acid (OA), an inhibitor of PP2A, caused cell rounding, reduction in F-actin assembly that links with beta1 integrin, and dissociation of IQGAP1-bound PP2A-AC from Rac-beta1 integrin. The dissociation of IQGAP1-PP2A-AC was accompanied by loss of F-actin gelating activity of Rac-beta1 integrin. In breast cancer MCF-7 cells, which possess PP2A-C but lack PP2A-A, IQGAP1 was not associated with Rac-beta1 integrin but with PP2A-C, with no distinct F-actin assembly that linked to Rac-beta1 integrin even before treatment with OA. We therefore propose that PP2A, especially PP2A-A, functions to maintain F-actin assembly to which beta1 integrin is anchored by recruitment of IQGAP1 to Rac-beta1 integrin.
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