ArticleMolecular biology of the cell2006
GSK-3 is activated by the tyrosine kinase Pyk2 during LPA1-mediated neurite retraction.
Article in Molecular biology of the cell, 2006. 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, 110 citations in OpenAlex.
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- Computational identification of phytochemicals as glycogen synthase kinase 3 beta (GSK3β) inhibitors for therapeutic applications in chronic diseases.Scientific reports · 2025Article
- Eyes Are the Windows to the Soul: Reviewing the Possible Use of the Retina to Indicate Traumatic Brain Injury.International journal of molecular sciences · 2025Review
- A Promising Drug Candidate as Potent Therapeutic Approach for Neuroinflammation and Its In Silico Justification of Chalcone Congeners: a Comprehensive Review.Molecular neurobiology · 2024Review
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- αeLife · 2023Article
- Alteration of Cellular Energy Metabolism through LPAR2-Axin2 Axis in Gastric Cancer.Biomolecules · 2022Article
- Glycogen Synthase Kinase 3β: A True Foe in Pancreatic Cancer.International journal of molecular sciences · 2022Review
- Decrypting a path based approach for identifying the interplay between PI3K and GSK3 signaling cascade from the perspective of cancer.Genes & diseases · 2022Review
- Alzheimer risk gene product Pyk2 suppresses tau phosphorylation and phenotypic effects of tauopathy.Molecular neurodegeneration · 2022Article
- Role of Glycogen Synthase Kinase-3 in Interferon-γ-Mediated Immune Hepatitis.International journal of molecular sciences · 2022Review
- Revisiting the Role of GSK3, A Modulator of Innate Immunity, in Idiopathic Inclusion Body Myositis.Cells · 2021Review
- The lipid phosphatase-like protein PLPPR1 associates with RhoGDI1 to modulate RhoA activation in response to axon growth inhibitory molecules.Journal of neurochemistry · 2021Article
- Review
- Deciphering the roles of glycogen synthase kinase 3 (GSK3) in the treatment of autism spectrum disorder and related syndromes.Molecular biology reports · 2021Review
- The role of glycogen synthase kinase 3 (GSK3) in cancer with emphasis on ovarian cancer development and progression: A comprehensive review.Bosnian journal of basic medical sciences · 2021Review
- The Non-receptor Tyrosine Kinase Pyk2 in Brain Function and Neurological and Psychiatric Diseases.Frontiers in synaptic neuroscience · 2021Review
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Glycogen synthase kinase-3 (GSK-3) is a multifunctional serine/threonine kinase that is usually inactivated by serine phosphorylation in response to extracellular cues. However, GSK-3 can also be activated by tyrosine phosphorylation, but little is known about the upstream signaling events and tyrosine kinase(s) involved. Here we describe a G protein signaling pathway leading to GSK-3 activation during lysophosphatidic acid (LPA)-induced neurite retraction. Using neuronal cells expressing the LPA(1) receptor, we show that LPA(1) mediates tyrosine phosphorylation and activation of GSK-3 with subsequent phosphorylation of the microtubule-associated protein tau via the G(i)-linked PIP(2) hydrolysis-Ca(2+) mobilization pathway. LPA concomitantly activates the Ca(2+)-dependent tyrosine kinase Pyk2, which is detected in a complex with GSK-3beta. Inactivation or knockdown of Pyk2 inhibits LPA-induced (but not basal) tyrosine phosphorylation of GSK-3 and partially inhibits LPA-induced neurite retraction, similar to what is observed following GSK-3 inhibition. Thus, Pyk2 mediates LPA(1)-induced activation of GSK-3 and subsequent phosphorylation of microtubule-associated proteins. Pyk2-mediated GSK-3 activation is initiated by PIP(2) hydrolysis and may serve to destabilize microtubules during actomyosin-driven neurite retraction.
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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.