title: Protein tyrosine phosphatase-like A regulates myoblast proliferation and differentiation through MyoG and the cell cycling signaling pathway.
abstract: Protein tyrosine phosphatase-like A (PTPLa) has been implicated in skeletal myogenesis and cardiogenesis. Mutations in PTPLa correlated with arrhythmogenic right ventricular dysplasia in humans and congenital centronuclear myopathy with severe hypotonia in dogs. The molecular mechanisms of PTPLa in myogenesis are unknown. In this report, we demonstrate that PTPLa is required for myoblast growth and differentiation. The cells lacking PTPLa remained immature and failed to differentiate into mature myotubes. The repressed MyoG expression was responsible for the impaired myoblast differentiation. Meanwhile, impeded cell growth, with an obvious S-phase arrest and compromised G(2)/M transition, was observed in PTPLa-deficient myoblasts. Further study demonstrated that the upregulation of cyclin D1 and cyclin E2 complexes, along with a compromised G(2)/M transition due to the decreased CDK1 (cyclin-dependent kinase 1) activity and upregulated p21, contributed to the mutant cell S-phase arrest and eventually led to the retarded cell growth. Finally, the transcriptional regulation of the PTPLa gene was explored. We identified PTPLa as a new target gene of the serum response factor (SRF). Skeletal- and cardiac-muscle-specific SRF knockouts resulted in significant decreases in PTPLa expression, suggesting a conserved transcriptional regulation of the PTPLa gene in mice.
authors: Texas A&M Health Science Center, Institute of Biosciences and Technology, Houston, Texas, USA.
authors: Xi
authors: X
authors: Lin
authors: Xiangsheng
authors: X
authors: Yang
authors: Qi
authors: Q
authors: Li
authors: Yanlin
authors: Y
authors: Ma
authors: Shuang
authors: S
authors: Cui
authors: Dacheng
authors: D
authors: He
authors: Xia
authors: X
authors: Lin
authors: Robert J
authors: RJ
authors: Schwartz
authors: Jiang
authors: J
authors: Chang
mesh_terms: D000818:Animals; D002453:Cell Cycle; D002454:Cell Differentiation; D002460:Cell Line; D049109:Cell Proliferation; D005786:Gene Expression Regulation; D051379:Mice; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000378:metabolism; D032446:Myoblasts / Q000166:cytology* / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D018008:Myogenin / Q000235:genetics / Q000378:metabolism*; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000378:metabolism*; D026362:Serum Response Factor / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
chemical_list: C503801:Myog protein, mouse; D018008:Myogenin; D026362:Serum Response Factor; C485760:Hacd1 protein, mouse; D017027:Protein Tyrosine Phosphatases