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- Multifaceted roles of Epac signaling in renal functions
3',5'-cyclic adenosine monophosphate (cAMP) is a fundamental secondary messenger capable of rapidly amplifying and propagating cellular signals in response to various extracellular stimuli cAMP plays a significant role in hormone-mediated regulation of renal fluid and electrolyte balance Impaired signaling of cAMP has been linked to a variety of pathological ramifications in the kidneys
- Regulation of Hormone-Sensitive Renal Phosphate Transport
The findings established the framework for the generally accepted view that the first six residues of PTH are necessary for activating adenylyl cyclase and the attendant formation of cyclic AMP (cAMP) and downstream signaling through PKA or exchange protein directly activated by cAMP (EPAC) Peptide fragments such as (PTH[7-34]) lacking this
- Regulation of sodium-proton exchanger isoform 3 (NHE3) by PKA . . . - PNAS
by EPAC kidney transporters T he Na H exchanger 3 (NHE3; SLC9A3) is expressed in the brushbordermembrane(BBM)ofrenalproximaltubules(PT) where it plays a major role in acid–base and extracellular volume regulation (1) This transporter is down-regulated by parathyroid hormone(PTH)anddopamine AcutetreatmentofratswithPTH
- The PTH Receptorsome and Transduction Pathways
While endogenous PTH in humans is an 84 amino acid polypeptide, synthetic peptides comprised of the first 34 amino acids are fully active for most if not all PTHR1-mediated biological responses The key determinants of hormone signaling and receptor binding reside within the N-terminal and C-terminal portions of the PTH(1–34) fragment, respectively
- Pathology Outlines - Parathyroid hormone
84 amino acids derived from cleavage of prepro parathyroid hormone (PTH); biologic activity due to 34 amino acids at amino terminus; other portions are inert but may give false positives in detection systems Binding of PTH to its receptor stimulates cAMP and phosphatidylinositol diphosphate Note: PTH related protein is rarely produced by
- Physiology of Parathyroid Hormone - Endocrinology and Metabolism Clinics
Parathyroid hormone (PTH) is the major secretory product of the chief cells of the parathyroid glands, and the human gene encoding PTH is located on chromosome 11 1 The translation product, preproPTH, is a 115-amino acid precursor peptide, that is extended at the amino (NH 2)-terminus by a leader (signal) or “pre” sequence that facilitates its entry into the secretory apparatus of the
- Endosomal signaling via cAMP in parathyroid hormone (PTH) type 1 . . .
The introduction of PTH backbone modifications, consisting of single α→β amino acid substitution (Liu et al , 2018), results in Gs-biased PTH analogs that induce cAMP production from the cell surface, but exhibit defective β-arrestin recruitment and fail to stimulate the generation of sustained endosomal cAMP (Liu et al , 2019)
- The Intricacies of Renal Phosphate Reabsorption—An Overview - MDPI
The N-terminal portion, especially the most N-terminal residues, is critical for PTH1R signalling Deletion of PTH Ser1 and Val2 significantly reduces cAMP production The C-terminal amino acids of the fragments (residues 15–34) bind to the PTH1R ECD and have a critical role in receptor selectivity and affinity
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