FCCC LOGO Faculty Publications
Joseph GA , Lu M , Radu M , Lee JK , Burden SJ , Chernoff J , Krauss RS
Group I Paks Promote Skeletal Myoblast Differentiation In Vivo and In Vitro
Mol Cell Biol. 2017 Feb 15;37(4)
PMID: 27920252    PMCID: PMC5288579    URL: https://www.ncbi.nlm.nih.gov/pubmed/27920252
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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.
Joseph, Giselle A Lu, Min Radu, Maria Lee, Jennifer K Burden, Steven J Chernoff, Jonathan Krauss, Robert S eng 2016/12/07 06:00 Mol Cell Biol. 2017 Feb 1;37(4). pii: e00222-16. doi: 10.1128/MCB.00222-16. Print 2017 Feb 15.