ArticleMolecular and cellular biology2009
Ras subcellular localization defines extracellular signal-regulated kinase 1 and 2 substrate specificity through distinct utilization of scaffold proteins.
Article in Molecular and cellular biology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.
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Who cites it
71 citing papers in PubMed, 112 citations in OpenAlex.
- ERK1/2 mitogen-activated protein kinase dimerization is essential for the regulation of cell motility.Molecular oncology · 2025Article
- SOS2 modulates the threshold of EGFR signaling to regulate osimertinib efficacy and resistance in lung adenocarcinoma.Molecular oncology · 2024Article
- Navigating the ERK1/2 MAPK Cascade.Biomolecules · 2023Review
- Kinase Suppressor of RAS 1 (KSR1) Maintains the Transformed Phenotype of BRAFV600E Mutant Human Melanoma Cells.International journal of molecular sciences · 2023Article
- The IQGAP scaffolds: Critical nodes bridging receptor activation to cellular signaling.The Journal of cell biology · 2023Review
- Scaffold coupling: ERK activation by trans-phosphorylation across different scaffold protein species.Science advances · 2023Article
- Cas9-mediated genome editing reveals a significant contribution of calcium signaling pathways to anhydrobiosis in Pv11 cells.Scientific reports · 2021Article
- Review
- Palmitoylation as a Key Regulator of Ras Localization and Function.Frontiers in molecular biosciences · 2021Review
- Anchorage-independent growth conditions reveal a differential SOS2 dependence for transformation and survival inSmall GTPases · 2021Article
- Spatial regulation and generation of diversity in signaling pathways.Journal of biosciences · 2021Review
- RAS Subcellular Localization Inversely Regulates Thyroid Tumor Growth and Dissemination.Cancers · 2020Article
- Characterisation of HRas local signal transduction networks using engineered site-specific exchange factors.Small GTPases · 2020Article
- VEGF-B signaling impairs endothelial glucose transcytosis by decreasing membrane cholesterol content.EMBO reports · 2020Article
- The ERK Pathway: Molecular Mechanisms and Treatment of Depression.Molecular neurobiology · 2019Review
- An emerging role for IQGAP1 in tight junction control.Small GTPases · 2018Review
- Ras and Rap Signal Bidirectional Synaptic Plasticity via Distinct Subcellular Microdomains.Neuron · 2018Article
- Comparative Transcriptome Analysis Reveals Growth-Related Genes in Juvenile Chinese Sea Cucumber, Russian Sea Cucumber, and Their Hybrids.Marine biotechnology (New York, N.Y.) · 2018Article
- Synaptic ERK2 Phosphorylates and Regulates Metabotropic Glutamate Receptor 1 In Vitro and in Neurons.Molecular neurobiology · 2017Article
- Local substrates of non-receptor tyrosine kinases at synaptic sites in neurons.Sheng li xue bao : [Acta physiologica Sinica] · 2017Review
11 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Subcellular localization influences the nature of Ras/extracellular signal-regulated kinase (ERK) signals by unknown mechanisms. Herein, we demonstrate that the microenvironment from which Ras signals emanate determines which substrates will be preferentially phosphorylated by the activated ERK1/2. We show that the phosphorylation of epidermal growth factor receptor (EGFr) and cytosolic phospholipase A(2) (cPLA(2)) is most prominent when ERK1/2 are activated from lipid rafts, whereas RSK1 is mainly activated by Ras signals from the disordered membrane. We present evidence indicating that the underlying mechanism of this substrate selectivity is governed by the participation of different scaffold proteins that distinctively couple ERK1/2, activated at defined microlocalizations, to specific substrates. As such, we show that for cPLA(2) activation, ERK1/2 activated at lipid rafts interact with KSR1, whereas ERK1/2 activated at the endoplasmic reticulum utilize Sef-1. To phosphorylate the EGFr, ERK1/2 activated at lipid rafts require the participation of IQGAP1. Furthermore, we demonstrate that scaffold usage markedly influences the biological outcome of Ras site-specific signals. These results disclose an unprecedented spatial regulation of ERK1/2 substrate specificity, dictated by the microlocalization from which Ras signals originate and by the selection of specific scaffold proteins.
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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.