000000184 001__ 184 000000184 005__ 20260422082640.0 000000184 0247_ $$2DOI$$a10.6083/M46T0JK6 000000184 037__ $$aETD 000000184 245__ $$aPhosphorylation of myosin-1c by cAMP-dependent protein kinase 000000184 260__ $$bOregon Health and Science University 000000184 269__ $$a2007 000000184 336__ $$aDissertation 000000184 502__ $$bPh.D. 000000184 520__ $$aSensory adaptation in inner ear hair cells depends on myosin‑1c (Myo1c), the molecular motor that regulates mechanotransduction channel sensitivity. This dissertation examines how protein kinase A (PKA) phosphorylation modulates Myo1c function. We demonstrate that Myo1c can be phosphorylated by PKA at serine 701 (S701) under specific calcium and calmodulin-dependent conditions, though phosphorylation is inefficient in cells. Mutations at S701 significantly alter ATPase activity, actin translocation velocity, and force production, indicating a critical role for this site in motor mechanics. Additional in vitro studies suggest that Myo1c tail domains contribute to efficient motility and force generation. Together, these findings reveal complex regulatory mechanisms controlling Myo1c activity and support a role for PKA signaling in hair cell adaptation. 000000184 540__ $$fCC BY 000000184 542__ $$fIn copyright - single owner 000000184 650__ $$aPhosphorylation$$024067 000000184 650__ $$aMedicine$$021959 000000184 650__ $$aMyosins$$022616 000000184 650__ $$aHair Cells, Auditory$$019810 000000184 650__ $$aProtein Serine-Threonine Kinases$$029894 000000184 650__ $$aPhosphorylation$$024067 000000184 650__ $$aCyclic AMP-Dependent Protein Kinases$$030307 000000184 650__ $$aEar, Inner$$021268 000000184 6531_ $$apka 000000184 691__ $$aSchool of Medicine$$041369 000000184 7001_ $$aMiller, Emilie$$uOregon Health and Science University$$041354 000000184 7201_ $$aGillespie, Peter$$uOregon Health and Science University$$041354$$7Personal$$eMentor 000000184 8564_ $$93d88d845-0a59-46fe-8bf7-8a0d835aeb34$$s3203624$$uhttps://digitalcollections.ohsu.edu/record/184/files/184_etd.pdf$$ePublic$$2d320fa5812fd71ab615b2153f88b0d81$$31 000000184 901__ $$a<p>These documents are archival records. They are retained for historical reference only. </p><p><b>Need an accessible version? Use the ‘Get Accessible Copy’ link above.</b></p> 000000184 905__ $$a/rest/prod/vh/53/wv/73/vh53wv730 000000184 909CO $$ooai:digitalcollections.ohsu.edu:184$$pstudent-work 000000184 956__ $$aGet Accessible Copy$$uhttps://ohsu.libwizard.com/f/requestaccessibledocument 000000184 980__ $$aTheses and Dissertations