ArticleMolecular biology of the cell2008
Integrin-mediated protein kinase A activation at the leading edge of migrating cells.
Article in Molecular biology of the cell, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
60 citing papers in PubMed, 96 citations in OpenAlex.
- PKIB facilitates bladder cancer proliferation and metastasis through mediation of HSP27 phosphorylation by PKA.Cell death & disease · 2025Article
- The focal adhesion protein talin is a mechanically gated A-kinase anchoring protein.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Fucosylation of HLA-DRB1 regulates CD4Nature cancer · 2023Article
- Loss of TDP-43 causes ectopic endothelial sprouting and migration defects through increasedFrontiers in cell and developmental biology · 2023Article
- Study of spatiotemporal regulation of kinase signaling using genetically encodable molecular tools.Current opinion in chemical biology · 2022Review
- cAMP-Dependent Signaling and Ovarian Cancer.Cells · 2022Review
- Phostensin enables lymphocyte integrin activation and population of peripheral lymphoid organs.The Journal of experimental medicine · 2022Article
- Article
- Protein Kinase A in cellular migration-Niche signaling of a ubiquitous kinase.Frontiers in molecular biosciences · 2022Review
- Breadth and Specificity in Pleiotropic Protein Kinase A Activity and Environmental Responses.Frontiers in cell and developmental biology · 2022Review
- Article
- cAMP Bursts Control T Cell Directionality by Actomyosin Cytoskeleton Remodeling.Frontiers in cell and developmental biology · 2021Article
- Phase Separation of a PKA Regulatory Subunit Controls cAMP Compartmentation and Oncogenic Signaling.Cell · 2020Article
- Protein kinase A activity is regulated by actomyosin contractility during cell migration and is required for durotaxis.Molecular biology of the cell · 2020Article
- The VASP-profilin1 (Pfn1) interaction is critical for efficient cell migration and is regulated by cell-substrate adhesion in a PKA-dependent manner.The Journal of biological chemistry · 2019Article
- Genetically Encoded Fluorescent Biosensors Illuminate the Spatiotemporal Regulation of Signaling Networks.Chemical reviews · 2018Review
- Switching Cyclic Nucleotide-Selective Activation of Cyclic Adenosine Monophosphate-Dependent Protein Kinase Holoenzyme Reveals Distinct Roles of Tandem Cyclic Nucleotide-Binding Domains.ACS chemical biology · 2017Article
- Fibronectin promotes directional persistence in fibroblast migration through interactions with both its cell-binding and heparin-binding domains.Scientific reports · 2017Article
- Protein kinase A regulates the Ras, Rap1 and TORC2 pathways in response to the chemoattractant cAMP inJournal of cell science · 2017Article
- Genetically encoded biosensors for visualizing live-cell biochemical activity at super-resolution.Nature methods · 2017Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
cAMP-dependent protein kinase A (PKA) is important in processes requiring localized cell protrusion, such as cell migration and axonal path finding. Here, we used a membrane-targeted PKA biosensor to reveal activation of PKA at the leading edge of migrating cells. Previous studies show that PKA activity promotes protrusion and efficient cell migration. In live migrating cells, membrane-associated PKA activity was highest at the leading edge and required ligation of integrins such as alpha4beta1 or alpha5beta1 and an intact actin cytoskeleton. alpha4 integrins are type I PKA-specific A-kinase anchoring proteins, and we now find that type I PKA is important for localization of alpha4beta1 integrin-mediated PKA activation at the leading edge. Accumulation of 3' phosphorylated phosphoinositides [PtdIns(3,4,5)P(3)] products of phosphatidylinositol 3-kinase (PI3-kinase) is an early event in establishing the directionality of migration; however, polarized PKA activation did not require PI3-kinase activity. Conversely, inhibition of PKA blocked accumulation of a PtdIns(3,4,5)P(3)-binding protein, the AKT-pleckstrin homology (PH) domain, at the leading edge; hence, PKA is involved in maintaining cell polarity during migration. In sum, we have visualized compartment-specific PKA activation in migrating cells and used it to reveal that adhesion-mediated localized activation of PKA is an early step in directional cell migration.
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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.