Requirement of protein phosphatase 2A for recruitment of IQGAP1 to Rac-bound beta1 integrin.
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.
Suzuki
Katsuo
K
Department of Biochemistry, Kanagawa Cancer Center Research Institute, Yokohama, Japan.
Chikamatsu
Yasuhiro
Y
Takahashi
Kazuhide
K
D000199:Actins / Q000378:metabolism; D001665:Binding Sites / Q000502:physiology; D001943:Breast Neoplasms / Q000378:metabolism; D002277:Carcinoma / Q000378:metabolism; D020134:Catalytic Domain / Q000502:physiology; D002448:Cell Adhesion / Q000502:physiology*; D002460:Cell Line; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005782:Gels / Q000378:metabolism; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism*; D046911:Macromolecular Substances; D019319:Okadaic Acid / Q000494:pharmacology; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology; D054648:Protein Phosphatase 2; D014783:Viscosity; D020744:rac GTP-Binding Proteins / Q000378:metabolism*; D020703:ras GTPase-Activating Proteins / Q000378:metabolism*
D000199:Actins; D004791:Enzyme Inhibitors; D005782:Gels; C101203:IQ motif containing GTPase activating protein 1; D019012:Integrin beta1; D046911:Macromolecular Substances; D020703:ras GTPase-Activating Proteins; D019319:Okadaic Acid; D010749:Phosphoprotein Phosphatases; D054648:Protein Phosphatase 2; D020744:rac GTP-Binding Proteins