Mirk/dyrk1B Is a Rho-induced Kinase Active in Skeletal Muscle Differentiation

摘要: The Rho family of small GTPases regulates numerous signaling pathways that control the organization cytoskeleton, transcription factor activity, and many aspects differentiation skeletal myoblasts. We now demonstrate kinase Mirk (minibrain-related kinase)/dyrk1B is induced by members Rho-family in myoblasts active muscle differentiation. an arginine-directed serine/threonine which expressed at elevated levels compared with other normal tissues. A promoter construct was activated when C2C12 were switched from growth to medium also RhoA, Cdc42, a lesser degree Rac1, but not MyoD or Myf5. protein increased following transient expression constitutively Cdc42-QL, RhoA-QL, Rac1-QL cells. High concentrations serum mitogens down-regulated through activation Ras-MEK-Erk pathway. As result, MEK1 inhibitor PD98059 switch medium. similar kinetics another Rho-induced gene, myogenin. 10-fold within 24-48 h after primary cultured cells; mouse L6 rat differentiate. Thus commitment stage myogenesis. Stable overexpression enabled fuse more rapidly placed function established depletion endogenous interfering RNA, prevented myoblast fusion into myotubes inhibited induction markers differentiation, including myogenin, fast twitch troponin T, myosin heavy chain. Other dyrk/minibrain/HIPK kinases lower organisms have been shown regulate transition participate development.