ArticleCell reports2018
Noonan Syndrome-Associated SHP2 Dephosphorylates GluN2B to Regulate NMDA Receptor Function.
Article in Cell reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
21 citing papers in PubMed, 37 citations in OpenAlex.
- Article
- Targeting Shp2 as a therapeutic strategy for neurodegenerative diseases.Translational psychiatry · 2025Review
- Rasopathy-Associated Mutation Ptpn11Cellular and molecular neurobiology · 2024Article
- SHP2 regulates GluA2 tyrosine phosphorylation required for AMPA receptor endocytosis and mGluR-LTD.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Neuronal Cannabinoid CBCancers · 2023Article
- NCK1 Modulates Neuronal Actin Dynamics and Promotes Dendritic Spine, Synapse, and Memory Formation.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Aberrant Cortical Layer Development of Brain Organoids Derived from Noonan Syndrome-iPSCs.International journal of molecular sciences · 2022Article
- Review
- Article
- Review
- Mitochondrial ROS control neuronal excitability and cell fate in frontotemporal dementia.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2022Article
- Modeling (not so) rare developmental disorders associated with mutations in the protein-tyrosine phosphatase SHP2.Frontiers in cell and developmental biology · 2022Review
- Integrated in silico MS-based phosphoproteomics and network enrichment analysis of RASopathy proteins.Orphanet journal of rare diseases · 2021Article
- Functional interactions of ion channels with the actin cytoskeleton: does coupling to dynamic actin regulate NMDA receptors?The Journal of physiology · 2021Review
- The Noonan syndrome-associated D61G variant of the protein tyrosine phosphatase SHP2 prevents synaptic down-scaling.The Journal of biological chemistry · 2020Article
- Regulation of NMDA glutamate receptor functions by the GluN2 subunits.Journal of neurochemistry · 2020Review
- Connecting the dots between SHP2 and glutamate receptors.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2020Review
- Article
- Excitatory neuron-specific SHP2-ERK signaling network regulates synaptic plasticity and memory.Science signaling · 2019Article
- Neogenin in Amygdala for Neuronal Activity and Information Processing.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2018Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Hyperactivating mutations in the non-receptor tyrosine phosphatase SHP2 cause Noonan syndrome (NS). NS is associated with cognitive deficits, but how hyperactivation of SHP2 in NS changes neuron function is not well understood. We find that mice bearing an NS-associated SHP2 allele (NS mice) have selectively impaired Schaffer collateral-CA1 NMDA (N-methyl-D-aspartate) receptor (NMDAR)-mediated neurotransmission and that residual NMDAR-mediated currents decay faster in NS mice because of reduced contribution of GluN1:GluN2B diheteromers. Consistent with altered GluN2B function, we identify GluN2B Y1252 as an NS-associated SHP2 substrate both in vitro and in vivo. Mutation of Y1252 does not alter recombinant GluN1:GluN2B receptor kinetics. Instead, phospho-Y1252 binds the actin-regulatory adaptor protein Nck2, and this interaction is required for proper NMDAR function. These results establish SHP2 and Nck2 as NMDAR regulatory proteins and strongly suggest that NMDAR dysfunction contributes to NS cognitive deficits.
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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.