ArticleMolecular endocrinology (Baltimore, Md.)2010
Signaling from the secretory granule to the nucleus: Uhmk1 and PAM.
Article in Molecular endocrinology (Baltimore, Md.), 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 51 citations in OpenAlex.
- Septins buffer actomyosin forces to protect the nucleus from genotoxic mechanical stress.The Journal of cell biology · 2026Article
- Tissue Damage in Rheumatoid Arthritis Is Genetically Linked to Low Peptidylglycine Alpha-Amidating Monooxygenase Activity in Synovial Fibroblasts.Arthritis & rheumatology (Hoboken, N.J.) · 2026Article
- Peptidylglycine alpha-amidating monooxygenase is important in mice for beta-cell cilia formation and insulin secretion but promotes diabetes risk through beta-cell independent mechanisms.Molecular metabolism · 2025Article
- Neuronal Network Inactivity Potentiates Neuropeptide Release from Mouse Cortical Neurons.eNeuro · 2025Article
- KIS, a target of SOX4, regulates the ID1-mediated enhancement of β-catenin to facilitate lung adenocarcinoma cell proliferation and metastasis.Journal of cancer research and clinical oncology · 2024Article
- Mobilisation of jerboa kidney gene networks during dehydration and opportunistic rehydration.iScience · 2023Article
- Germline loss-of-functionmedRxiv : the preprint server for health sciences · 2023Article
- UHMK1-dependent phosphorylation of Cajal body protein coilin alters 5-FU sensitivity in colon cancer cells.Cell communication and signaling : CCS · 2022Article
- Extracellular vesicles derived from ascitic fluid enhance growth and migration of ovarian cancer cells.Scientific reports · 2021Article
- Long Non-coding RNA EBLN3P Regulates UHMK1 Expression by Sponging miR-323a-3p and Promotes Colorectal Cancer Progression.Frontiers in medicine · 2021Article
- UHMK1 promotes gastric cancer progression through reprogramming nucleotide metabolism.The EMBO journal · 2020Article
- PERK-mediated expression of peptidylglycine α-amidating monooxygenase supports angiogenesis in glioblastoma.Oncogenesis · 2020Article
- A pH-sensitive luminal His-cluster promotes interaction of PAM with V-ATPase along the secretory and endocytic pathways of peptidergic cells.Journal of cellular physiology · 2019Article
- Changes in Corticotrope Gene Expression Upon Increased Expression of Peptidylglycine α-Amidating Monooxygenase.Endocrinology · 2018Article
- Alternate promoter usage generates two subpopulations of the neuronal RhoGEF Kalirin-7.Journal of neurochemistry · 2017Article
- Kalirin is required for BDNF-TrkB stimulated neurite outgrowth and branching.Neuropharmacology · 2016Article
- 60 YEARS OF POMC: From POMC and α-MSH to PAM, molecular oxygen, copper, and vitamin C.Journal of molecular endocrinology · 2016Review
- O-Glycosylation of a Secretory Granule Membrane Enzyme Is Essential for Its Endocytic Trafficking.The Journal of biological chemistry · 2016Article
- Early eukaryotic origins for cilia-associated bioactive peptide-amidating activity.Journal of cell science · 2016Article
- Kalirin-9 and Kalirin-12 Play Essential Roles in Dendritic Outgrowth and Branching.Cerebral cortex (New York, N.Y. : 1991) · 2015Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Neurons and endocrine cells package peptides in secretory granules (large dense-core vesicles) for storage and stimulated release. Studies of peptidylglycine alpha-amidating monooxygenase (PAM), an essential secretory granule membrane enzyme, revealed a pathway that can relay information from secretory granules to the nucleus, resulting in alterations in gene expression. The cytosolic domain (CD) of PAM, a type 1 membrane enzyme essential for the production of amidated peptides, is basally phosphorylated by U2AF homology motif kinase 1 (Uhmk1) and other Ser/Thr kinases. Proopiomelanocortin processing in AtT-20 corticotrope tumor cells was increased when Uhmk1 expression was reduced. Uhmk1 was concentrated in the nucleus, but cycled rapidly between nucleus and cytosol. Endoproteolytic cleavage of PAM releases a soluble CD fragment that localizes to the nucleus. Localization of PAM-CD to the nucleus was decreased when PAM-CD with phosphomimetic mutations was examined and when active Uhmk1 was simultaneously overexpressed. Membrane-tethering Uhmk1 did not eliminate its ability to exclude PAM-CD from the nucleus, suggesting that cytosolic Uhmk1 could cause this response. Microarray analysis demonstrated the ability of PAM to increase expression of a small subset of genes, including aquaporin 1 (Aqp1) in AtT-20 cells. Aqp1 mRNA levels were higher in wild-type mice than in mice heterozygous for PAM, indicating that a similar relationship occurs in vivo. Expression of PAM-CD also increased Aqp1 levels whereas expression of Uhmk1 diminished Aqp1 expression. The outlines of a pathway that ties secretory granule metabolism to the transcriptome are thus apparent.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.