Cyclin G-associated kinase regulates protein phosphatase 2A by phosphorylation of its B'γ subunit

• Published in: Cell cycle (Georgetown, Tex.) Vol. 11; no. 3; pp. 604 - 616
• Main Authors: Naito, Yoko, Shimizu, Hiroyuki, Kasama, Takashi, Sato, Jun, Tabara, Hiroe, Okamoto, Ayumi, Yabuta, Norikazu, Nojima, Hiroshi
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 01.02.2012
• Subjects: Amino Acid Sequence; Animals; Binding; Biology; Bioscience; Calcium; Cancer; Cell; Cell Line, Tumor; Centrosome - metabolism; Checkpoint Kinase 2; Chromosomes - metabolism; Cycle; DNA Damage; Gamma Rays; HeLa Cells; Histones - metabolism; Humans; Intracellular Signaling Peptides and Proteins - antagonists & inhibitors; Intracellular Signaling Peptides and Proteins - genetics; Intracellular Signaling Peptides and Proteins - metabolism; Landes; Mice; Mitosis; Molecular Sequence Data; Organogenesis; Phosphorylation; Protein Phosphatase 2 - metabolism; Protein Subunits - metabolism; Protein-Serine-Threonine Kinases - antagonists & inhibitors; Protein-Serine-Threonine Kinases - genetics; Protein-Serine-Threonine Kinases - metabolism; Proteins; RNA Interference; RNA, Small Interfering - metabolism; Signal Transduction
• ISSN: 1538-4101; 1551-4005
• DOI: 10.4161/cc.11.3.19114

Protein phosphatase 2A (PP2A) bearing the B'γ (= B'α/B56γ1/PR61γ) subunit is recruited to dephosphorylation targets by cyclin G. We demonstrate here that cyclin G-associated kinase (GAK), a component of the GAK/B'γ/cyclin G complex, directly phosphorylates the B'γ-Thr104 residue and regulates PP2A activity. Indeed, an anti-B'γ-pT104 antibody detected immunofluorescence signals at the chromosome and centrosome during mitosis; these signals were reduced by siRNA-mediated GAK knockdown. After DNA damage by γ-irradiation, the chromosome signals formed foci that colocalized with a DNA double-strand break (DSB) marker H2AX-pS139 (γH2AX) and CHK2-pT68. Moreover, B'γ-pT104 enhanced PP2A holoenzyme assembly and PP2A activity, as shown by the results of an in vitro phosphatase assay. These results suggest a novel role for GAK as a regulator of dephosphorylation events under the control of the PP2A B'γ subunit.