title: Group I Paks Promote Skeletal Myoblast Differentiation In Vivo and In Vitro.
abstract: Skeletal myogenesis is regulated by signal transduction, but the factors and mechanisms involved are not well understood. The group I Paks Pak1 and Pak2 are related protein kinases and direct effectors of Cdc42 and Rac1. Group I Paks are ubiquitously expressed and specifically required for myoblast fusion in Drosophila We report that both Pak1 and Pak2 are activated during mammalian myoblast differentiation. One pathway of activation is initiated by N-cadherin ligation and involves the cadherin coreceptor Cdo with its downstream effector, Cdc42. Individual genetic deletion of Pak1 and Pak2 in mice has no overt effect on skeletal muscle development or regeneration. However, combined muscle-specific deletion of Pak1 and Pak2 results in reduced muscle mass and a higher proportion of myofibers with a smaller cross-sectional area. This phenotype is exacerbated after repair to acute injury. Furthermore, primary myoblasts lacking Pak1 and Pak2 display delayed expression of myogenic differentiation markers and myotube formation. These results identify Pak1 and Pak2 as redundant regulators of myoblast differentiation in vitro and in vivo and as components of the promyogenic Ncad/Cdo/Cdc42 signaling pathway.
authors.affiliation: Department of Cell, Developmental, and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.|Graduate School of Biological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Giselle A
authors.initials: GA
authors.lastname: Joseph
authors.affiliation: Department of Cell, Developmental, and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.|Graduate School of Biological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Min
authors.initials: M
authors.lastname: Lu
authors.affiliation: Cancer Biology Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Radu
authors.affiliation: Skirball Institute of Biomolecular Medicine, NYU Medical School, New York, New York, USA.
authors.forename: Jennifer K
authors.initials: JK
authors.lastname: Lee
authors.affiliation: Skirball Institute of Biomolecular Medicine, NYU Medical School, New York, New York, USA.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Burden
authors.affiliation: Cancer Biology Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Chernoff
authors.affiliation: Department of Cell, Developmental, and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, New York, USA Robert.Krauss@mssm.edu.|Graduate School of Biological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Krauss
mesh_terms: D000818:Animals; D015820:Cadherins / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line; D004789:Enzyme Activation; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D024510:Muscle Development; D032448:Myoblasts, Skeletal / Q000166:cytology* / Q000201:enzymology*; D041681:NIH 3T3 Cells; D009469:Neuromuscular Junction / Q000378:metabolism; D009929:Organ Size; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012038:Regeneration; D015398:Signal Transduction; D013569:Synapses / Q000378:metabolism; D054462:p21-Activated Kinases / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D015820:Cadherins; D015815:Cell Adhesion Molecules; C515905:Pak1 protein, mouse; C515909:Pak2 protein, mouse; D051057:Proto-Oncogene Proteins c-akt; D054462:p21-Activated Kinases; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Pak; cell adhesion; cell differentiation; myogenesis; regeneration; signal transduction