Spatial bias in cAMP generation determines biological responses to PTH type 1 receptor activation
Alex D. White, Karina A. Peña, Lisa J. Clark, Christian Santa Maria, Shi Liu, Frédéric Jean‐Alphonse, Ji Young Lee, Saifei Lei, Zhiqiang Cheng, Chia‐Ling Tu, Fei Fang, Nicholas Szeto, Thomas J. Gardella, Kunhong Xiao, Samuel H. Gellman, İvet Bahar, Ieva Sutkevičiu̅tė, Wenhan Chang, Jean‐Pierre Vilardaga
Abstract
and in bone formation in mice. Thus, similar amounts of cAMP generated by PTHR for similar lengths of time in different cellular locations, plasma membrane and endosomes, mediate distinct physiological responses. These results unveil subcellular signaling location as a means to achieve specificity in PTHR-mediated biological outcomes and raise the prospect of rational drug design based upon spatiotemporal manipulation of GPCR signaling.
Topics & Concepts
EndosomeG protein-coupled receptorParathyroid hormoneCell biologyReceptorParathyroid hormone receptorSignal transductionInternalizationChemistryCell signalingBiologyInternal medicineHormone receptorBiochemistryCalciumMedicineBreast cancerCancerOrganic chemistryReceptor Mechanisms and SignalingProtein Kinase Regulation and GTPase SignalingIon channel regulation and function