Recent Advances in the Cyclic AMP Signaling Pathway

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cell Signaling".

Deadline for manuscript submissions: closed (30 June 2023) | Viewed by 2153

Special Issue Editor


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Guest Editor
Department of Integrative Biology & Pharmacology, Texas Therapeutics Institute, University of Texas Health Science Center at Houston, Houston, TX 7000, USA
Interests: cAMP-mediated cell signaling; drug discovery; molecular pharmacology

Special Issue Information

Dear Colleagues,

The cyclic AMP second messenger is an ancient and universal stress-response signal conserved from bacterium to human. This important molecular switch regulates a myriad of important biological processes under both physiological and pathological conditions. Not surprisingly, current pharmaceutical medications target cyclic nucleotide signaling pathways more than any other pathway.

Intracellular cAMP is generated from ATP by the action of adenylate cyclases (ACs) in response to the activation of guanine-nucleotide-binding proteins (G proteins) prompted by the binding of extracellular ligands to G-protein-coupled receptors (GPCRs). Opposing the action of ACs, cyclic nucleotide phosphodiesterases (PDEs) inactivate cAMP by breaking the phosphodiester bond. In mammals, at least five families of cAMP effector proteins are known: the classic protein kinase A (PKA), the cyclic nucleotide regulated ion channels (CNG and HCN), the exchange proteins directly activated by cAMP (EPAC1 and EPAC2), the Popeye domain containing (POPDC) proteins, and the cyclic nucleotide receptor involved in sperm function (CRIS). These diverse signaling molecules control all facets of cellular function, including but not limited to cell growth, differentiation, secretion, adhesion and motility, gene transcription, protein translation, etc. In this Special Issue, we welcome the submission of high-quality and up-to-date original research or review articles covering the broad field of basic, translational, and clinical research related to the cAMP signaling pathway.

Prof. Dr. Xiaodong Cheng
Guest Editor

Manuscript Submission Information

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Keywords

  • cAMP
  • EPAC
  • PKA
  • GPCR
  • G protein
  • adenylate cyclase
  • phosphodiesterase (PDE)
  • A-kinase anchoring protein (AKAP)
  • drug discovery
  • signaling cross-talk

Published Papers (1 paper)

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Research

20 pages, 6405 KiB  
Article
The Prostaglandin E2 Receptor EP4 Promotes Vascular Neointimal Hyperplasia through Translational Control of Tenascin C via the cAMP/PKA/mTORC1/rpS6 Pathway
by Hu Xu, Bingying Fang, Chengzhen Bao, Xiuhui Mao, Chunhua Zhu, Lan Ye, Qian Liu, Yaqing Li, Chunxiu Du, Hang Qi, Xiaoyan Zhang and Youfei Guan
Cells 2022, 11(17), 2720; https://doi.org/10.3390/cells11172720 - 31 Aug 2022
Cited by 3 | Viewed by 1784
Abstract
Prostaglandin E2 (PGE2) is an important metabolite of arachidonic acid which plays a crucial role in vascular physiology and pathophysiology via its four receptors (EP1-4). However, the role of vascular smooth muscle cell (VSMC) EP4 in neointimal hyperplasia is largely unknown. Here we [...] Read more.
Prostaglandin E2 (PGE2) is an important metabolite of arachidonic acid which plays a crucial role in vascular physiology and pathophysiology via its four receptors (EP1-4). However, the role of vascular smooth muscle cell (VSMC) EP4 in neointimal hyperplasia is largely unknown. Here we showed that VSMC-specific deletion of EP4 (VSMC-EP4) ameliorated, while VSMC-specific overexpression of human EP4 promoted, neointimal hyperplasia in mice subjected to femoral artery wire injury or carotid artery ligation. In vitro studies revealed that pharmacological activation of EP4 promoted, whereas inhibition of EP4 suppressed, proliferation and migration of primary-cultured VSMCs. Mechanically, EP4 significantly increased the protein expression of tenascin C (TN-C), a pro-proliferative and pro-migratory extracellular matrix protein, at the translational level. Knockdown of TN-C markedly suppressed EP4 agonist-induced VSMC proliferation and migration. Further studies uncovered that EP4 upregulated TN-C protein expression via the PKA/mTORC1/Ribosomal protein S6 (rpS6) pathway. Together, our findings demonstrate that VSMC EP4 increases TN-C protein expression to promote neointimal hyperplasia via the PKA-mTORC1-rpS6 pathway. Therefore, VSMC EP4 may represent a potential therapeutic target for vascular restenosis. Full article
(This article belongs to the Special Issue Recent Advances in the Cyclic AMP Signaling Pathway)
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