ArticleThe Journal of biological chemistry2010
Pituitary adenylate cyclase-activating polypeptide (PACAP)/PAC1HOP1 receptor activation coordinates multiple neurotrophic signaling pathways: Akt activation through phosphatidylinositol 3-kinase gamma and vesicle endocytosis for neuronal survival.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 92 citations in OpenAlex.
- Structural basis of β-arrestin coupling and transducer selectivity in PAC1R.Acta pharmacologica Sinica · 2026Article
- β-arrestin1 orchestrates endosomal signaling to regulate translational control of circadian light entrainment.Communications biology · 2026Article
- Role of the Transcription Factor CREB in Ethanol-Induced Endoplasmic Reticulum Stress and Apoptosis in PC12 Cells.Biology · 2025Article
- Deconvolution Analysis of G and F-Actin Unfolding: Insights into the Thermal Stability and Structural Modifications Induced by PACAP.International journal of molecular sciences · 2025Article
- Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) and Sudden Infant Death Syndrome: A Potential Model for Investigation.International journal of molecular sciences · 2023Review
- Circulating PACAP levels are associated with increased amygdala-default mode network resting-state connectivity in posttraumatic stress disorder.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2023Article
- Novel Fluorescently Labeled PACAP and VIP Highlight Differences between Peptide Internalization and Receptor Pharmacology.ACS pharmacology & translational science · 2023Article
- cAMP-induced decrease in cell-surface laminin receptor and cellular prion protein attenuates amyloid-β uptake and amyloid-β-induced neuronal cell death.FEBS letters · 2022Article
- Immunomodulatory Role of Neuropeptides in the Cornea.Biomedicines · 2022Review
- Targeting VIP and PACAP Receptor Signaling: New Insights into Designing Drugs for the PACAP Subfamily of Receptors.International journal of molecular sciences · 2022Review
- GPCR Intracellular Loop Regulation of Beta-Arrestin-Mediated Endosomal Signaling Dynamics.Journal of molecular neuroscience : MN · 2022Article
- Pituitary adenylate cyclase-activating polypeptide receptor activation in the hypothalamus recruits unique signaling pathways involved in energy homeostasis.American journal of physiology. Endocrinology and metabolism · 2022Article
- Signal Transduction by VIP and PACAP Receptors.Biomedicines · 2022Review
- The Protective Effects of Endogenous PACAP in Oxygen-Induced Retinopathy.Journal of molecular neuroscience : MN · 2021Article
- The G Protein-Coupled Receptor PAC1 Regulates Transactivation of the Receptor Tyrosine Kinase HER3.Journal of molecular neuroscience : MN · 2021Article
- PAC1 Receptor Internalization and Endosomal MEK/ERK Activation Is Essential for PACAP-Mediated Neuronal Excitability.Journal of molecular neuroscience : MN · 2021Review
- Prefrontal cortex PACAP signaling: organization and role in stress regulation.Stress (Amsterdam, Netherlands) · 2021Article
- Alterations of Nigral Dopamine Levels in Parkinson's Disease after Environmental Enrichment and PACAP Treatment in Aging Rats.Life (Basel, Switzerland) · 2021Article
- Signaling pathways and promoter regions that mediate pituitary adenylate cyclase activating polypeptide (PACAP) self-regulation in gonadotrophs.Molecular and cellular endocrinology · 2020Article
- Splice-specific deficiency of the PTSD-associated gene PAC1 leads to a paradoxical age-dependent stress behavior.Scientific reports · 2020Article
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
MAPK and Akt pathways are predominant mediators of trophic signaling for many neuronal systems. Among the vasoactive intestinal peptide/secretin/glucagon family of related peptides, pituitary adenylate cyclase-activating polypeptide (PACAP) binding to specific PAC(1) receptor isoforms can engage multiple signaling pathways and promote neuroprotection through mechanisms that are not well understood. Using a primary sympathetic neuronal system, the current studies demonstrate that PACAP activation of PAC(1)HOP1 receptors engages both MAPK and Akt neurotrophic pathways in an integrated program to facilitate neuronal survival after growth factor withdrawal. PACAP not only stimulated prosurvival ERK1/2 and ERK5 activation but also abrogated SAPK/JNK and p38 MAPK signaling in parallel. In contrast to the potent and rapid effects of PACAP in ERK1/2 phosphorylation, PACAP stimulated Akt phosphorylation in a late phase of PAC(1)HOP1 receptor signaling. From inhibitor and immunoprecipitation analyses, the PACAP/PAC(1)HOP1 receptor-mediated Akt responses did not represent transactivation mechanisms but appeared to depend on G alpha(q)/phosphatidylinositol 3-kinase gamma activity and vesicular internalization pathways. Phosphatidylinositol 3-kinase gamma-selective inhibitors blocked PACAP-stimulated Akt phosphorylation in primary neuronal cultures and in PAC(1)HOP1-overexpressing cell lines; RNA interference-mediated knockdown of the receptor effectors attenuated PACAP-mediated Akt activation. Similarly, perturbation of endocytic pathways also blocked Akt phosphorylation. Between ERK and Akt pathways, PACAP-stimulated Akt signaling was the primary cascade that attenuated cultured neuron apoptosis after growth factor withdrawal. The partitioning of PACAP-mediated Akt signaling in endosomes may be a key mechanism contributing to the high spatial and temporal specificity in signal transduction necessary for survival pathways.
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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.