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Initiation of human myoblast differentiation via dephosphorylation of Kir2.1 K+ channels at tyrosine 242

Published in Development. 2008, vol. 135, no. 5, p. 859-67
Abstract Myoblast differentiation is essential to skeletal muscle formation and repair. The earliest detectable event leading to human myoblast differentiation is an upregulation of Kir2.1 channel activity, which causes a negative shift (hyperpolarization) of the resting potential of myoblasts. After exploring various mechanisms, we found that this upregulation of Kir2.1 was due to dephosphorylation of the channel itself. Application of genistein, a tyrosine kinase inhibitor, increased Kir2.1 activity and triggered the differentiation process, whereas application of bpV(Phen), a tyrosine phosphatase inhibitor, had the opposite effects. We could show that increased Kir2.1 activity requires dephosphorylation of tyrosine 242; replacing this tyrosine in Kir2.1 by a phenylalanine abolished inhibition by bpV(Phen). Finally, we found that the level of tyrosine phosphorylation in endogenous Kir2.1 channels is considerably reduced during differentiation when compared with proliferation. We propose that Kir2.1 channels are already present at the membrane of proliferating, undifferentiated human myoblasts but in a silent state, and that Kir2.1 tyrosine 242 dephosphorylation triggers differentiation.
Keywords Amino Acid SequenceBiotinylationCell Culture TechniquesCell DifferentiationCell DivisionCell Membrane/physiologyDNA/geneticsElectrophysiologyElectroporationGene Expression RegulationHumansMyoblasts/cytology/physiologyPhosphotyrosine/metabolismPotassium Channels Inwardly Rectifying/chemistry/genetics/metabolismTransfectionTyrosine/metabolismUp-Regulation
PMID: 18216177
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Other version: http://dev.biologists.org/cgi/content/full/135/5/859
Research groups Translocation des protéines à travers les membranes (169)
Culture Primaire de myoblastes humains (208)
(ISO format)
HINARD, Valérie et al. Initiation of human myoblast differentiation via dephosphorylation of Kir2.1 K+ channels at tyrosine 242. In: Development, 2008, vol. 135, n° 5, p. 859-67. https://archive-ouverte.unige.ch/unige:751

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Deposited on : 2009-02-11

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