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Ascl1‐induced neuronal differentiation of P19 cells requires expression of a specific inhibitor protein of cyclic AMP‐dependent protein kinase

dc.contributor.authorHuang, Holly S.en_US
dc.contributor.authorTurner, David L.en_US
dc.contributor.authorThompson, Robert C.en_US
dc.contributor.authorUhler, Michael D.en_US
dc.date.accessioned2012-03-16T15:59:20Z
dc.date.available2013-05-01T17:24:41Zen_US
dc.date.issued2012-03en_US
dc.identifier.citationHuang, Holly S.; Turner, David L.; Thompson, Robert C.; Uhler, Michael D. (2012). "Ascl1‐induced neuronal differentiation of P19 cells requires expression of a specific inhibitor protein of cyclic AMP‐dependent protein kinase." Journal of Neurochemistry 120(5). <http://hdl.handle.net/2027.42/90302>en_US
dc.identifier.issn0022-3042en_US
dc.identifier.issn1471-4159en_US
dc.identifier.urihttps://hdl.handle.net/2027.42/90302
dc.description.abstractcAMP‐dependent protein kinase (PKA) plays a critical role in nervous system development by modulating sonic hedgehog and bone morphogenetic protein signaling. In the current studies, P19 embryonic carcinoma cells were neuronally differentiated by expression of the proneural basic helix‐loop‐helix transcription factor Ascl1. After expression of Ascl1, but prior to expression of neuronal markers such as microtubule associated protein 2 and neuronal β‐tubulin, P19 cells demonstrated a large, transient increase in both mRNA and protein for the endogenous protein kinase inhibitor (PKI)β. PKIβ‐targeted shRNA constructs both reduced the levels of PKIβ expression and blocked the neuronal differentiation of P19 cells. This inhibition of differentiation was rescued by transfection of a shRNA‐resistant expression vector for the PKIβ protein, and this rescue required the PKA‐specific inhibitory sequence of the PKIβ protein. PKIβ played a very specific role in the Ascl1‐mediated differentiation process as other PKI isoforms were unable to rescue the deficit conferred by shRNA‐mediated knockdown of PKIβ. Our results define a novel requirement for PKIβ and its inhibition of PKA during neuronal differentiation of P19 cells.en_US
dc.publisherBlackwell Publishing Ltden_US
dc.publisherWiley Periodicals, Inc.en_US
dc.subject.otherShRNAen_US
dc.subject.otherCyclic AMPen_US
dc.subject.otherDifferentiationen_US
dc.titleAscl1‐induced neuronal differentiation of P19 cells requires expression of a specific inhibitor protein of cyclic AMP‐dependent protein kinaseen_US
dc.typeArticleen_US
dc.rights.robotsIndexNoFollowen_US
dc.subject.hlbsecondlevelNeurosciencesen_US
dc.subject.hlbtoplevelHealth Sciencesen_US
dc.description.peerreviewedPeer Revieweden_US
dc.contributor.affiliationumNeuroscience Graduate Program, University of Michigan, Ann Arbor, Michigan, USAen_US
dc.contributor.affiliationumMolecular and Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, Michigan, USAen_US
dc.contributor.affiliationumDepartment of Biological Chemistry, University of Michigan, Ann Arbor, Michigan, USAen_US
dc.contributor.affiliationumDepartment of Psychiatry, University of Michigan, Ann Arbor, Michigan, USAen_US
dc.description.bitstreamurlhttp://deepblue.lib.umich.edu/bitstream/2027.42/90302/1/j.1471-4159.2011.07332.x.pdf
dc.identifier.doi10.1111/j.1471-4159.2011.07332.xen_US
dc.identifier.sourceJournal of Neurochemistryen_US
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dc.owningcollnameInterdisciplinary and Peer-Reviewed


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