ArticleThe Journal of biological chemistry2009
Spatial distribution of protein kinase A activity during cell migration is mediated by A-kinase anchoring protein AKAP Lbc.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 57 citations in OpenAlex.
- PKIB facilitates bladder cancer proliferation and metastasis through mediation of HSP27 phosphorylation by PKA.Cell death & disease · 2025Article
- cAMP-Dependent Signaling and Ovarian Cancer.Cells · 2022Review
- Article
- Protein Kinase A in cellular migration-Niche signaling of a ubiquitous kinase.Frontiers in molecular biosciences · 2022Review
- GPCRs thatSmall GTPases · 2022Review
- Region-Specific Transcriptional Control of Astrocyte Function Oversees Local Circuit Activities.Neuron · 2020Article
- Protein kinase A activity is regulated by actomyosin contractility during cell migration and is required for durotaxis.Molecular biology of the cell · 2020Article
- cAMP-dependent activation of the Rac guanine exchange factor P-REX1 by type I protein kinase A (PKA) regulatory subunits.The Journal of biological chemistry · 2019Article
- Article
- Potential Role of Mic60/Mitofilin in Parkinson's Disease.Frontiers in neuroscience · 2018Review
- Protein kinase A regulates the Ras, Rap1 and TORC2 pathways in response to the chemoattractant cAMP inJournal of cell science · 2017Article
- A novel spiroindoline targets cell cycle and migration via modulation of microtubule cytoskeleton.Molecular and cellular biochemistry · 2017Article
- Methods to Study Mrp4-containing Macromolecular Complexes in the Regulation of Fibroblast Migration.Journal of visualized experiments : JoVE · 2016Article
- Dynamic regulation of neutrophil polarity and migration by the heterotrimeric G protein subunits Gαi-GTP and Gβγ.Science signaling · 2016Article
- Determination of cell uptake pathways for tumor inhibitor lysyl oxidase propeptide.Molecular oncology · 2016Article
- cAMP Promotes Cell Migration Through Cell Junctional Complex Dynamics and Actin Cytoskeleton Remodeling: Implications in Skin Wound Healing.Stem cells and development · 2015Article
- PKA and actin play critical roles as downstream effectors in MRP4-mediated regulation of fibroblast migration.Cellular signalling · 2015Article
- Anchoring of protein kinase A by ERM (ezrin-radixin-moesin) proteins is required for proper netrin signaling through DCC (deleted in colorectal cancer).The Journal of biological chemistry · 2015Article
- Förster resonance energy transfer - an approach to visualize the spatiotemporal regulation of macromolecular complex formation and compartmentalized cell signaling.Biochimica et biophysica acta · 2014Review
- cAMP-PKA inhibition of SK3 channel reduced both Ca2+ entry and cancer cell migration by regulation of SK3-Orai1 complex.Pflugers Archiv : European journal of physiology · 2014Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Protein kinase A (PKA) has been suggested to be spatially regulated in migrating cells due to its ability to control signaling events that are critical for polarized actin cytoskeletal dynamics. Here, using the fluorescence resonance energy transfer-based A-kinase activity reporter (AKAR1), we find that PKA activity gradients form with the strongest activity at the leading edge and are restricted to the basal surface in migrating cells. The existence of these gradients was confirmed using immunocytochemistry using phospho-PKA substrate antibodies. This observation holds true for carcinoma cells migrating randomly on laminin-1 or stimulated to migrate on collagen I with lysophosphatidic acid. Phosphodiesterase inhibition allows the formation of PKA activity gradients; however, these gradients are no longer polarized. PKA activity gradients are not detected when a non-phosphorylatable mutant of AKAR1 is used, if PKA activity is inhibited with H-89 or protein kinase inhibitor, or when PKA anchoring is perturbed. We further find that a specific A-kinase anchoring protein, AKAP-Lbc, is a major contributor to the formation of these gradients. In summary, our data show that PKA activity gradients are generated at the leading edge of migrating cells and provide additional insight into the mechanisms of PKA regulation of cell motility.
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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.