title: PKN2 and Cdo interact to activate AKT and promote myoblast differentiation.
abstract: Skeletal myogenesis is coordinated by multiple signaling pathways that control cell adhesion/migration, survival and differentiation accompanied by muscle-specific gene expression. A cell surface protein Cdo is involved in cell contact-mediated promyogenic signals through activation of p38MAPK and AKT. Protein kinase C-related kinase 2 (PKN2/PRK2) is implicated in regulation of various biological processes, including cell migration, adhesion and death. It has been shown to interact with and inhibit AKT thereby inducing cell death. This led us to investigate the role of PKN2 in skeletal myogenesis and the crosstalk between PKN2 and Cdo. Like Cdo, PKN2 was upregulated in C2C12 myoblasts during differentiation and decreased in cells with Cdo depletion caused by shRNA or cultured on integrin-independent substratum. This decline of PKN2 levels resulted in diminished AKT activation during myoblast differentiation. Consistently, PKN2 overexpression-enhanced C2C12 myoblast differentiation, whereas PKN2-depletion impaired it, without affecting cell survival. PKN2 formed complexes with Cdo, APPL1 and AKT via its C-terminal region and this interaction appeared to be important for induction of AKT activity as well as myoblast differentiation. Furthermore, PKN2-enhanced MyoD-responsive reporter activities by mediating the recruitment of BAF60c and MyoD to the myogenin promoter. Taken together, PKN2 has a critical role in cell adhesion-mediated AKT activation during myoblast differentiation.
authors.affiliation: Research Center for Cell Fate Control, College of Pharmacy, Department of Cell Therapy, Sookmyung Women's University, Seoul, Republic of Korea.
authors.forename: Sang-Jin
authors.initials: SJ
authors.lastname: Lee
authors.affiliation: Research Center for Cell Fate Control, College of Pharmacy, Department of Cell Therapy, Sookmyung Women's University, Seoul, Republic of Korea.
authors.forename: Jeongmi
authors.initials: J
authors.lastname: Hwang
authors.affiliation: Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Samsung Biomedical Research Institute, Suwon, Republic of Korea.
authors.forename: Hyeon-Ju
authors.initials: HJ
authors.lastname: Jeong
authors.affiliation: Research Center for Cell Fate Control, College of Pharmacy, Department of Cell Therapy, Sookmyung Women's University, Seoul, Republic of Korea.
authors.forename: Miran
authors.initials: M
authors.lastname: Yoo
authors.affiliation: Research Center for Cell Fate Control, College of Pharmacy, Department of Cell Therapy, Sookmyung Women's University, Seoul, Republic of Korea.
authors.forename: Ga-Yeon
authors.initials: GY
authors.lastname: Go
authors.affiliation: Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Samsung Biomedical Research Institute, Suwon, Republic of Korea.
authors.forename: Jae-Rin
authors.initials: JR
authors.lastname: Lee
authors.affiliation: Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Samsung Biomedical Research Institute, Suwon, Republic of Korea.
authors.forename: Young-Eun
authors.initials: YE
authors.lastname: Leem
authors.affiliation: Research Center for Epigenome Regulation, School of Pharmacy, Department of Biochemistry and Molecular Biology, Sungkyunkwan University, Suwon, Republic of Korea.
authors.forename: Jong Woo
authors.initials: JW
authors.lastname: Park
authors.affiliation: College of Pharmacy, Department of Biochemistry, Dankook University, Cheonan, Republic of Korea.
authors.forename: Dong-Wan
authors.initials: DW
authors.lastname: Seo
authors.affiliation: Research Center for Cell Fate Control, College of Pharmacy, Department of Cell Therapy, Sookmyung Women's University, Seoul, Republic of Korea.
authors.forename: Yong Kee
authors.initials: YK
authors.lastname: Kim
authors.affiliation: Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Samsung Biomedical Research Institute, Suwon, Republic of Korea.
authors.forename: Myong-Joon
authors.initials: MJ
authors.lastname: Hahn
authors.affiliation: Research Center for Epigenome Regulation, School of Pharmacy, Department of Biochemistry and Molecular Biology, Sungkyunkwan University, Suwon, Republic of Korea.
authors.forename: Jeung-Whan
authors.initials: JW
authors.lastname: Han
authors.affiliation: Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Samsung Biomedical Research Institute, Suwon, Republic of Korea.
authors.forename: Jong-Sun
authors.initials: JS
authors.lastname: Kang
authors.affiliation: Research Center for Cell Fate Control, College of Pharmacy, Department of Cell Therapy, Sookmyung Women's University, Seoul, Republic of Korea.
authors.forename: Gyu-Un
authors.initials: GU
authors.lastname: Bae
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002454:Cell Differentiation; D002460:Cell Line; D004789:Enzyme Activation; D017930:Genes, Reporter; D051379:Mice; D017570:MyoD Protein / Q000378:metabolism; D032446:Myoblasts / Q000166:cytology* / Q000378:metabolism*; D011485:Protein Binding; D011493:Protein Kinase C / Q000737:chemistry / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D020798:Two-Hybrid System Techniques; D015854:Up-Regulation
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C510733:Appl1 protein, mouse; C510744:Cdon protein, mouse; D015815:Cell Adhesion Molecules; D017570:MyoD Protein; C061570:protein kinase N; D051057:Proto-Oncogene Proteins c-akt; D011493:Protein Kinase C