ArticleJournal of cell science2015
Spatial control of Shoc2-scaffold-mediated ERK1/2 signaling requires remodeling activity of the ATPase PSMC5.
Article in Journal of cell science, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 29 citations in OpenAlex.
- Signaling scaffold Shoc2 regulates lymphangiogenesis by suppressing mTORC1-mediated IFN responses.Cell death and differentiation · 2026Article
- Strengthening the Role ofInternational journal of molecular sciences · 2025Article
- The expression of congenital Shoc2 variants induces AKT-dependent crosstalk activation of the ERK1/2 pathway.Human molecular genetics · 2024Article
- Exploiting bacterial effector proteins to uncover evolutionarily conserved antiviral host machinery.PLoS pathogens · 2024Article
- Exploiting Bacterial Effector Proteins to Uncover Evolutionarily Conserved Antiviral Host Machinery.bioRxiv : the preprint server for biology · 2024Article
- Shoc2 controls ERK1/2-driven neural crest development by balancing components of the extracellular matrix.Developmental biology · 2022Article
- Pan-cancer analysis identifies proteasome 26S subunit, ATPase (PSMC) family genes, and related signatures associated with prognosis, immune profile, and therapeutic response in lung adenocarcinoma.Frontiers in genetics · 2022Article
- The role of USP7 in the Shoc2-ERK1/2 signaling axis and Noonan-like syndrome with loose anagen hair.Journal of cell science · 2021Article
- Article
- A Leucine-Rich Repeat Protein Provides a SHOC2 the RAS Circuit: a Structure-Function Perspective.Molecular and cellular biology · 2021Review
- The leucine-rich repeat signaling scaffolds Shoc2 and Erbin: cellular mechanism and role in disease.The FEBS journal · 2021Review
- PSMC5 Promotes Proliferation and Metastasis of Colorectal Cancer by Activating Epithelial-Mesenchymal Transition Signaling and Modulating Immune Infiltrating Cells.Frontiers in cell and developmental biology · 2021Article
- Article
- SHOC2 is associated with the survival of breast cancer cells and has prognostic value for patients with breast cancer.Molecular medicine reports · 2020Article
- Single-domain antibodies for functional targeting of the signaling scaffold Shoc2.Molecular immunology · 2020Article
- VCP/p97 controls signals of the ERK1/2 pathway transmitted via the Shoc2 scaffolding complex: novel insights into IBMPFD pathology.Molecular biology of the cell · 2019Article
- The FBXW7-SHOC2-Raptor Axis Controls the Cross-Talks between the RAS-ERK and mTORC1 Signaling Pathways.Cell reports · 2019Article
- Hematopoietic and neural crest defects in zebrafish shoc2 mutants: a novel vertebrate model for Noonan-like syndrome.Human molecular genetics · 2019Article
- Erbin Suppresses KSR1-Mediated RAS/RAF Signaling and Tumorigenesis in Colorectal Cancer.Cancer research · 2018Article
- Inositol phosphates and phosphoinositides activate insulin-degrading enzyme, while phosphoinositides also mediate binding to endosomes.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
The scaffold protein Shoc2 accelerates activity of the ERK1 and ERK2 (ERK1/2, also known as MAPK3 and MAPK1) pathway. Mutations in Shoc2 result in Noonan-like RASopathy, a developmental disorder with a wide spectrum of symptoms. The amplitude of the ERK1/2 signals transduced through the complex is fine-tuned by the HUWE1-mediated ubiquitylation of Shoc2 and its signaling partner RAF-1. Here, we provide a mechanistic basis of how ubiquitylation of Shoc2 and RAF-1 is controlled. We demonstrate that the newly identified binding partner of Shoc2, the (AAA+) ATPase PSMC5, triggers translocation of Shoc2 to endosomes. At the endosomes, PSMC5 displaces the E3 ligase HUWE1 from the scaffolding complex to attenuate ubiquitylation of Shoc2 and RAF-1. We show that a RASopathy mutation that changes the subcellular distribution of Shoc2 leads to alterations in Shoc2 ubiquitylation due to the loss of accessibility to PSMC5. In summary, our results demonstrate that PSMC5 is a new and important player involved in regulating ERK1/2 signal transmission through the remodeling of Shoc2 scaffold complex in a spatially-defined manner.
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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.