ArticlePloS one2014
Protein kinase d isoforms differentially modulate cofilin-driven directed cell migration.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 38 citations in OpenAlex.
- Pan-cancer landscape of protein kinase D3: An integrative TCGA multi-omics analysis of clinical, molecular, and immunological roles.PloS one · 2026Article
- PKD3 localizes to late endosomes to maintain Rab7-dependent endolysosomal homeostasis.iScience · 2025Article
- Potential Prognostic Role of Protein Kinase D Isoforms in Head and Neck Cancers.International journal of molecular sciences · 2024Article
- PRKD3 promotes proliferation of liver cancer cells: a downstream proteomics profiling study.American journal of translational research · 2024Article
- Protein Kinase D3 (PKD3) Requires Hsp90 for Stability and Promotion of Prostate Cancer Cell Migration.Cells · 2023Article
- Membrane trafficking in breast cancer progression: protein kinase D comes into play.Frontiers in cell and developmental biology · 2023Review
- Cofilin activation in pancreatic acinar cells plays a pivotal convergent role for mediating CCK-stimulated enzyme secretion and growth.Frontiers in physiology · 2023Article
- Decoding the Cardiac Actions of Protein Kinase D Isoforms.Molecular pharmacology · 2021Review
- Review
- Multifaceted Functions of Protein Kinase D in Pathological Processes and Human Diseases.Biomolecules · 2021Review
- Unraveling the Molecular Tumor-Promoting Regulation of Cofilin-1 in Pancreatic Cancer.Cancers · 2021Article
- The oncogenic role of protein kinase D3 in cancer.Journal of Cancer · 2021Review
- Oncogenic functions of protein kinase D2 and D3 in regulating multiple cancer-related pathways in breast cancer.Cancer medicine · 2019Article
- The phosphorylation status of PIP5K1C at serine 448 can be predictive for invasive ductal carcinoma of the breast.Oncotarget · 2018Article
- P21-activated kinase 4 in pancreatic acinar cells is activated by numerous gastrointestinal hormones/neurotransmitters and growth factors by novel signaling, and its activation stimulates secretory/growth cascades.American journal of physiology. Gastrointestinal and liver physiology · 2018Article
- Protein kinase D1: gatekeeper of the epithelial phenotype and key regulator of cancer metastasis?British journal of cancer · 2018Article
- Function and Regulation of Protein Kinase D in Oxidative Stress: A Tale of Isoforms.Oxidative medicine and cellular longevity · 2018Review
- Lysophosphatidic acid via LPA-receptor 5/protein kinase D-dependent pathways induces a motile and pro-inflammatory microglial phenotype.Journal of neuroinflammation · 2017Article
- Identification of the PAK4 interactome reveals PAK4 phosphorylation of N-WASP and promotion of Arp2/3-dependent actin polymerization.Oncotarget · 2017Article
- Src-mediated tyrosine phosphorylation of Protein Kinase D2 at focal adhesions regulates cell adhesion.Scientific reports · 2017Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
backgroundProtein kinase D (PKD) enzymes regulate cofilin-driven actin reorganization and directed cell migration through both p21-activated kinase 4 (PAK4) and the phosphatase slingshot 1L (SSH1L). The relative contributions of different endogenous PKD isoforms to both signaling pathways have not been elucidated, sufficiently. METHODOLOGY/PRINCIPAL
findingsWe here analyzed two cell lines (HeLa and MDA-MB-468) that express the subtypes protein kinase D2 (PKD2) and protein kinase D3 (PKD3). We show that under normal growth conditions both isoforms can form a complex, in which PKD3 is basally-active and PKD2 is inactive. Basal activity of PKD3 mediates PAK4 activity and downstream signaling, but does not significantly inhibit SSH1L. This signaling constellation was required for facilitating directed cell migration. Activation of PKD2 and further increase of PKD3 activity leads to additional phosphorylation and inhibition of endogenous SSH1L. Net effect is a dramatic increase in phospho-cofilin and a decrease in cell migration, since now both PAK4 and SSH1L are regulated by the active PKD2/PKD3 complex. CONCLUSIONS/SIGNIFICANCE: Our data suggest that PKD complexes provide an interface for both cofilin regulatory pathways. Dependent on the activity of involved PKD enzymes signaling can be balanced to guarantee a functional cofilin activity cycle and increase cell migration, or imbalanced to decrease cell migration. Our data also provide an explanation of how PKD isoforms mediate different effects on directed 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.