000000633 001__ 633
000000633 005__ 20260226133050.0
000000633 0247_ $$2DOI$$a10.6083/M42R3PPD
000000633 037__ $$aETD
000000633 245__ $$aThe spatial control of Rap1 and Epac proteins
000000633 260__ $$bOregon Health and Science University
000000633 269__ $$a2010
000000633 336__ $$aDissertation
000000633 502__ $$bPh.D.
000000633 520__ $$aRap1, a small GTPase regulating proliferation, differentiation, and adhesion, is activated by cAMP‑responsive guanine nucleotide exchange factors (GEFs) Epac1 and Epac2. This work tests the hypothesis that Rap1 signaling is spatially regulated through compartment‑specific targeting of these GEFs. Epac2 interacts with Ras‑GTP, which recruits it to the plasma membrane and enables efficient Rap1 activation when combined with cAMP signaling. In PC12 cells, this coordination enhances ERK activation and neurite outgrowth. Proteomic analysis revealed that Epac1 associates with nuclear pore complex components, including Ran, through a unique RA domain, enabling Rap1 activation at the nuclear envelope. Together, these findings show that Epac1 and Epac2 localize to distinct subcellular compartments via Ran and Ras interactions, allowing cAMP to activate discrete Rap1 pools and diversify downstream signaling.
000000633 540__ $$fCC BY
000000633 542__ $$fIn copyright - single owner
000000633 650__ $$arap1 GTP-Binding Proteins$$032734
000000633 650__ $$aGuanine Nucleotide Exchange Factors$$032584
000000633 650__ $$aran GTP-Binding Protein$$032820
000000633 650__ $$aOncogene Protein p21(ras)$$028578
000000633 650__ $$aRats
000000633 650__ $$aPC12 Cells$$029345
000000633 650__ $$aGuanosine Triphosphate$$019779
000000633 650__ $$aMonomeric GTP-Binding Proteins$$032494
000000633 650__ $$aMice$$036842
000000633 650__ $$aHumans
000000633 6531_ $$aepac1 protein
000000633 6531_ $$aepac2 protein
000000633 691__ $$aSchool of Medicine$$041369
000000633 692__ $$aDepartment of Cell, Developmental and Cancer Biology$$041399
000000633 7001_ $$aLiu, Chang$$uOregon Health and Science University$$041354
000000633 7201_ $$aStork, Philip$$uOregon Health and Science University$$041354$$7Personal$$eAdvisor$$eMentor
000000633 8564_ $$9e8e552b7-fef4-4380-b20c-ae0000bc62ab$$s3165510$$uhttps://digitalcollections.ohsu.edu/record/633/files/634_etd.pdf$$ePublic$$27df6f6e43ae662ea821798731f820adc$$31
000000633 905__ $$a/rest/prod/kd/17/cs/88/kd17cs888
000000633 909CO $$ooai:digitalcollections.ohsu.edu:633$$pstudent-work
000000633 956__ $$aGet Accessible Copy$$uhttps://ohsu.libwizard.com/f/requestaccessibledocument
000000633 980__ $$aTheses and Dissertations