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dc.contributor.authorLi, Yunping
dc.contributor.authorReznichenko, Maya
dc.contributor.authorTribe, Rachel M.
dc.contributor.authorHess, Philip E.
dc.contributor.authorTaggart, Michael
dc.contributor.authorKim, HakRim
dc.contributor.authorDeGnore, Jon P.
dc.contributor.authorGangopadhyay, Samudra
dc.contributor.authorMorgan, Kathleen G.
dc.date.accessioned2011-02-22T00:40:31Z
dc.date.issued2009
dc.identifier.citationLi, Yunping, Maya Reznichenko, Rachel M. Tribe, Philip E. Hess, Michael Taggart, HakRim Kim, Jon P. DeGnore, Samudra Gangopadhyay, and Kathleen G. Morgan. 2009. Stretch activates human myometrium via ERK, caldesmon and focal adhesion signaling. PLoS ONE 4(10): e7489.en_US
dc.identifier.issn1932-6203en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:4728748
dc.description.abstractAn incomplete understanding of the molecular mechanisms responsible for myometrial activation from the quiescent pregnant state to the active contractile state during labor has hindered the development of effective therapies for preterm labor. Myometrial stretch has been implicated clinically in the initiation of labor and the etiology of preterm labor, but the molecular mechanisms involved in the human have not been determined. We investigated the mechanisms by which gestation-dependent stretch contributes to myometrial activation, by using human uterine samples from gynecologic hysterectomies and Cesarean sections. Here we demonstrate that the Ca requirement for activation of the contractile filaments in human myometrium increases with caldesmon protein content during gestation and that an increase in caldesmon phosphorylation can reverse this inhibitory effect during labor. By using phosphotyrosine screening and mass spectrometry of stretched human myometrial samples, we identify 3 stretch-activated focal adhesion proteins, FAK, p130Cas, and alpha actinin. FAK-Y397, which signals integrin engagement, is constitutively phosphorylated in term human myometrium whereas FAK-Y925, which signals downstream ERK activation, is phosphorylated during stretch. We have recently identified smooth muscle Archvillin (SmAV) as an ERK regulator. A newly produced SmAV-specific antibody demonstrates gestation-specific increases in SmAV protein levels and stretch-specific increases in SmAV association with focal adhesion proteins. Thus, whereas increases in caldesmon levels suppress human myometrium contractility during pregnancy, stretch-dependent focal adhesion signaling, facilitated by the ERK activator SmAV, can contribute to myometrial activation. These results suggest that focal adhesion proteins may present new targets for drug discovery programs aimed at regulation of uterine contractility.en_US
dc.language.isoen_USen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.isversionofdoi:10.1371/journal.pone.0007489en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC2759504/pdf/en_US
dash.licenseLAA
dc.titleStretch Activates Human Myometrium via ERK, Caldesmon and Focal Adhesion Signalingen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalPLoS ONEen_US
dash.depositing.authorLi, Yunping
dc.date.available2011-02-22T00:40:31Z
dash.affiliation.otherHMS^Anaesthesia- Beth Israel-Deaconessen_US
dash.affiliation.otherHMS^Anaesthesia- Beth Israel-Deaconessen_US
dc.identifier.doi10.1371/journal.pone.0007489*
dash.contributor.affiliatedLi, Yunping
dash.contributor.affiliatedHess, Philip


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