title: Role for the pleckstrin homology domain-containing protein CKIP-1 in phosphatidylinositol 3-kinase-regulated muscle differentiation.
abstract: In this work, we report the implication of the pleckstrin homology (PH) domain-containing protein CKIP-1 in phosphatidylinositol 3-kinase (PI3-K)-regulated muscle differentiation. CKIP-1 is upregulated during muscle differentiation in C2C12 cells. We show that CKIP-1 binds to phosphatidylinositol 3-phosphate through its PH domain and localizes to the plasma membrane in a PI3-K-dependent manner. Activation of PI3-K by insulin or expression of an active form of PI3-K p110 induces a rapid translocation of CKIP-1 to the plasma membrane. Conversely, expression of the 3-phosphoinositide phosphatase myotubularin or PI3-K inhibition by LY294002, wortmannin, or mutant p85 abolishes CKIP-1 binding to the membrane. Upon induction of differentiation in low-serum medium, CKIP-1 overexpression in C2C12 myoblasts first promotes proliferation and then stimulates the expression of myogenin and cell fusion in a manner reminiscent of the dual positive effect of insulin-like growth factors on muscle cells. Interference with the PI3-K pathway impedes the effect of CKIP-1 on C2C12 cell differentiation. Finally, silencing of CKIP-1 by RNA interference abolishes proliferation and delays myogenin expression. Altogether, these data strongly implicate CKIP-1 as a new component of PI3-K signaling in muscle differentiation.
authors.affiliation: Equipe de Biologie des Regulations Cellulaires, LBMC, CNRS UMR5665, ENS Lyon, IFR128 BioSciences Lyon-Gerland, Lyon, France.
authors.forename: Alexias
authors.initials: A
authors.lastname: Safi
authors.forename: Marie
authors.initials: M
authors.lastname: Vandromme
authors.forename: Sabine
authors.initials: S
authors.lastname: Caussanel
authors.forename: Laure
authors.initials: L
authors.lastname: Valdacci
authors.forename: Dominique
authors.initials: D
authors.lastname: Baas
authors.forename: Marc
authors.initials: M
authors.lastname: Vidal
authors.forename: Gilbert
authors.initials: G
authors.lastname: Brun
authors.forename: Laurent
authors.initials: L
authors.lastname: Schaeffer
authors.forename: Evelyne
authors.initials: E
authors.lastname: Goillot
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology*; D002455:Cell Division / Q000502:physiology; D002462:Cell Membrane / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D009132:Muscles / Q000196:embryology* / Q000378:metabolism; D032446:Myoblasts / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D017434:Protein Structure, Tertiary
chemical_list: D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; C408877:PLEKHO1 protein, human; D019869:Phosphatidylinositol 3-Kinases