ArticleMolecular brain2010
Pyk2 uncouples metabotropic glutamate receptor G protein signaling but facilitates ERK1/2 activation.
Article in Molecular brain, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 48 citations in OpenAlex.
- ATF4 Modulates Group 1 mGluR-Dependent molecular signaling, hippocampal plasticity and behavior.Molecular psychiatry · 2026Article
- Synaptic proteome diversity is shaped by the levels of glutamate receptors and their regulatory proteins.Nature communications · 2025Article
- PYK2 senses calcium through a disordered dimerization and calmodulin-binding element.Communications biology · 2022Article
- Group I mGluRs in Therapy and Diagnosis of Parkinson's Disease: Focus on mGluR5 Subtype.Biomedicines · 2022Review
- The Implication of STEP in Synaptic Plasticity and Cognitive Impairments in Alzheimer's Disease and Other Neurological Disorders.Frontiers in cell and developmental biology · 2021Review
- The Non-receptor Tyrosine Kinase Pyk2 in Brain Function and Neurological and Psychiatric Diseases.Frontiers in synaptic neuroscience · 2021Review
- Insights on the Functional Interaction between Group 1 Metabotropic Glutamate Receptors (mGluRI) and ErbB Receptors.International journal of molecular sciences · 2020Review
- Silent Allosteric Modulation of mGluR5 Maintains Glutamate Signaling while Rescuing Alzheimer's Mouse Phenotypes.Cell reports · 2017Article
- Metabotropic glutamate receptor subtype 5: molecular pharmacology, allosteric modulation and stimulus bias.British journal of pharmacology · 2016Review
- Orchestrated activation of mGluR5 and CB1 promotes neuroprotection.Molecular brain · 2016Article
- Role of Spinophilin in Group I Metabotropic Glutamate Receptor Endocytosis, Signaling, and Synaptic Plasticity.The Journal of biological chemistry · 2016Article
- Oligomers of Amyloid β Prevent Physiological Activation of the Cellular Prion Protein-Metabotropic Glutamate Receptor 5 Complex by Glutamate in Alzheimer Disease.The Journal of biological chemistry · 2016Article
- Metabotropic glutamate receptor 5 couples cellular prion protein to intracellular signalling in Alzheimer's disease.Brain : a journal of neurology · 2016Article
- Group I Metabotropic Glutamate Receptor Interacting Proteins: Fine-Tuning Receptor Functions in Health and Disease.Current neuropharmacology · 2016Review
- Ca(2+)/calmodulin-dependent protein kinase II interacts with group I metabotropic glutamate and facilitates receptor endocytosis and ERK1/2 signaling: role of β-amyloid.Molecular brain · 2015Article
- Glutamate receptors function as scaffolds for the regulation of β-amyloid and cellular prion protein signaling complexes.Molecular brain · 2015Review
- Location-dependent signaling of the group 1 metabotropic glutamate receptor mGlu5.Molecular pharmacology · 2014Review
- Agonist-dependent signaling by group I metabotropic glutamate receptors is regulated by association with lipid domains.The Journal of biological chemistry · 2013Article
- Metabotropic glutamate receptor 5 is a coreceptor for Alzheimer aβ oligomer bound to cellular prion protein.Neuron · 2013Article
- Non-receptor-tyrosine kinases integrate fast glucocorticoid signaling in hippocampal neurons.The Journal of biological chemistry · 2013Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Group I metabotropic glutamate receptors (mGluRs) are coupled via Galphaq/11 to the activation of phospholipase Cbeta, which hydrolyzes membrane phospholipids to form inositol 1,4,5 trisphosphate and diacylglycerol. This results in the release of Ca2+ from intracellular stores and the activation of protein kinase C. The activation of Group I mGluRs also results in ERK1/2 phosphorylation. We show here, that the proline-rich tyrosine kinase 2 (Pyk2) interacts with both mGluR1 and mGluR5 and is precipitated with both receptors from rat brain. Pyk2 also interacts with GST-fusion proteins corresponding to the second intracellular loop and the distal carboxyl-terminal tail domains of mGluR1a. Pyk2 colocalizes with mGluR1a at the plasma membrane in human embryonic kidney (HEK293) cells and with endogenous mGluR5 in cortical neurons. Pyk2 overexpression in HEK293 results in attenuated basal and agonist-stimulated inositol phosphate formation in mGluR1 expressing cells and involves a mechanism whereby Pyk2 displaces Galphaq/11 from the receptor. The activation of endogenous mGluR1 in primary mouse cortical neuron stimulates ERK1/2 phosphorylation. Treatments that prevent Pyk2 phosphorylation in cortical neurons, and the overexpression of Pyk2 dominant-negative and catalytically inactive Pyk2 mutants in HEK293 cells, prevent ERK1/2 phosphorylation. The Pyk2 mediated activation of ERK1/2 phosphorylation is also Src-, calmodulin- and protein kinase C-dependent. Our data reveal that Pyk2 couples the activation mGluRs to the mitogen-activated protein kinase pathway even though it attenuates mGluR1-dependent G protein signaling.
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