ArticleThe Journal of biological chemistry2011
Protein kinase Cα promotes cell migration through a PDZ-dependent interaction with its novel substrate discs large homolog 1 (DLG1).
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
36 citing papers in PubMed, 1 synthesis or guideline pooled it, 61 citations in OpenAlex.
- Downregulation of hsa-microRNA-204-5p and identification of its potential regulatory network in non-small cell lung cancer: RT-qPCR, bioinformatic- and meta-analyses.Respiratory research · 2020Pooled it
- A chemigenetic endogenous Ras activity biosensor for live-cell pharmacology.Nature chemical biology · 2026Article
- The relationship between Connexin 43 (Cx43) and partner protein, human discs large homologue-1 (Dlg1) during wound closure in keratinocytes.Cell and tissue research · 2026Article
- Small extracellular vesicles promote invadopodia activity in glioblastoma cells in a therapy-dependent manner.Cellular oncology (Dordrecht, Netherlands) · 2023Article
- The human discs large protein 1 interacts with and maintains connexin 43 at the plasma membrane in keratinocytes.Journal of cell science · 2023Article
- Spatiotemporal Regulation of FMNL2 by N-Terminal Myristoylation and C-Terminal Phosphorylation Drives Rapid Filopodia Formation.Biomolecules · 2023Article
- Enhanced activity of Alzheimer disease-associated variant of protein kinase Cα drives cognitive decline in a mouse model.Nature communications · 2022Article
- S-acylation-dependent membrane microdomain localization of the regulatory Kvβ2.1 subunit.Cellular and molecular life sciences : CMLS · 2022Article
- Protein Kinase C Life Cycle: Explained Through Systems Biology Approach.Frontiers in physiology · 2022Article
- Conventional protein kinase C in the brain: repurposing cancer drugs for neurodegenerative treatment?Neuronal signaling · 2021Review
- The complexities of PKCα signaling in cancer.Advances in biological regulation · 2021Review
- Electrostatic plasma membrane targeting contributes to Dlg function in cell polarity and tumorigenesis.Development (Cambridge, England) · 2021Article
- PKCα is required for Akt-mTORC1 activation in non-small cell lung carcinoma (NSCLC) with EGFR mutation.Oncogene · 2019Article
- Comparative Analysis of the Transcriptome and Proteome during Mouse Placental Development.Journal of proteome research · 2019Article
- FRETting over postsynaptic PKC signaling.Nature neuroscience · 2018Article
- Protein kinase Cα gain-of-function variant in Alzheimer's disease displays enhanced catalysis by a mechanism that evades down-regulation.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Article
- Conventional protein kinase C in the brain: 40 years later.Neuronal signaling · 2017Review
- PKCα diffusion and translocation are independent of an intact cytoskeleton.Scientific reports · 2017Article
- The Functional and Molecular Properties, Physiological Functions, and Pathophysiological Roles of GluN2A in the Central Nervous System.Molecular neurobiology · 2017Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 5 institutions in 2 countries.
Funding
Abstract
Protein scaffolds maintain precision in kinase signaling by coordinating kinases with components of specific signaling pathways. Such spatial segregation is particularly important in allowing specificity of signaling mediated by the 10-member family of protein kinase C (PKC) isozymes. Here we identified a novel interaction between PKCα and the Discs large homolog (DLG) family of scaffolds that is mediated by a class I C-terminal PDZ (PSD-95, disheveled, and ZO1) ligand unique to this PKC isozyme. Specifically, use of a proteomic array containing 96 purified PDZ domains identified the third PDZ domains of DLG1/SAP97 and DLG4/PSD95 as interaction partners for the PDZ binding motif of PKCα. Co-immunoprecipitation experiments verified that PKCα and DLG1 interact in cells by a mechanism dependent on an intact PDZ ligand. Functional assays revealed that the interaction of PKCα with DLG1 promotes wound healing; scratch assays using cells depleted of PKCα and/or DLG1 have impaired cellular migration that is no longer sensitive to PKC inhibition, and the ability of exogenous PKCα to rescue cellular migration is dependent on the presence of its PDZ ligand. Furthermore, we identified Thr-656 as a novel phosphorylation site in the SH3-Hook region of DLG1 that acts as a marker for PKCα activity at this scaffold. Increased phosphorylation of Thr-656 is correlated with increased invasiveness in non-small cell lung cancer lines from the NCI-60, consistent with this phosphorylation site serving as a marker of PKCα-mediated invasion. Taken together, these data establish the requirement of scaffolding to DLG1 for PKCα to promote cellular migration.
Indexed as
Identifiers
What OpenQuestion holds
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.