Mitotic dissociation of IQGAP1 from Rac-bound beta1-integrin is mediated by protein phosphatase 2A.
Assembly of F-actin that links with beta1-integrin during the G1 phase of cell cycle is released from beta1-integrin and disrupted at mitosis. However, it remains unclear how F-actin assembly to which beta1-integrin anchors is cell cycle-dependently regulated. We show that beta1-integrin was co-immunoprecipitated and co-localized with a small GTPase Rac and its effector IQGAP1, along with PP2A-AC, in HME cells during G1. When the cells were accumulated to G2/M, the co-immunoprecipitation or co-localization of IQGAP1 and PP2A-AC with beta1-integrin was lost, leaving Rac bound to beta1-integrin. The dissociated IQGAP1 was co-immunoprecipitated with the concomitantly dissociated PP2A-A and -C, indicating the complex formation among the proteins in G2/M cells. Falling ball viscometric assays revealed that only IQGAP1-bound beta1-integrin-Rac in G1 cells exhibited an enhanced F-actin cross-linking activity. The results suggest that the mitotic loss of F-actin assembly to which beta1-integrin anchors is due to PP2A-mediated dissociation of IQGAP1 from Rac-bound beta1-integrin.
Nakajima
Eri
E
Department of Biochemistry, Kanagawa Cancer Center Research Institute, 1-1-2 Nakao, Asahi-ku, Yokohama 241-0815, Japan.
Suzuki
Katsuo
K
Takahashi
Kazuhide
K
D000199:Actins / Q000378:metabolism*; D001940:Breast / Q000166:cytology / Q000378:metabolism*; D002460:Cell Line; D016193:G1 Phase / Q000502:physiology*; D016195:G2 Phase / Q000502:physiology*; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism*; D008938:Mitosis / Q000502:physiology; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D054648:Protein Phosphatase 2; D020744:rac GTP-Binding Proteins / Q000378:metabolism*; D020703:ras GTPase-Activating Proteins / Q000378:metabolism*
D000199:Actins; C101203:IQ motif containing GTPase activating protein 1; D019012:Integrin beta1; D020703:ras GTPase-Activating Proteins; D010749:Phosphoprotein Phosphatases; D054648:Protein Phosphatase 2; D020744:rac GTP-Binding Proteins