ArticleMolecular and cellular biology2010
Protein kinase Cdelta-mediated phosphorylation of phospholipase D controls integrin-mediated cell spreading.
Article in Molecular and cellular biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 29 citations in OpenAlex.
- Proteomic profiling reveals CEACAM6 function in driving gallbladder cancer aggressiveness through integrin receptor, PRKCD and AKT/ERK signaling.Cell death & disease · 2024Article
- Increased phospholipase D activity contributes to tumorigenesis in prostate cancer cell models.Molecular and cellular biochemistry · 2020Article
- Mammalian phospholipase D: Function, and therapeutics.Progress in lipid research · 2020Review
- PLD-dependent phosphatidic acid microdomains are signaling platforms for podosome formation.Scientific reports · 2019Article
- Cardiomyocytes Sense Matrix Rigidity through a Combination of Muscle and Non-muscle Myosin Contractions.Developmental cell · 2018Article
- Phospholipase D inhibitors reduce human prostate cancer cell proliferation and colony formation.British journal of cancer · 2018Article
- Visualization of Neuregulin 1 ectodomain shedding reveals its local processing in vitro and in vivo.Scientific reports · 2016Article
- PKCδ regulates integrin αVβ3 expression and transformed growth of K-ras dependent lung cancer cells.Oncotarget · 2016Article
- Mechanism of enzymatic reaction and protein-protein interactions of PLD from a 3D structural model.Cellular signalling · 2015Article
- The molecular basis of leukocyte adhesion involving phosphatidic acid and phospholipase D.The Journal of biological chemistry · 2014Article
- Phospholipase D signaling pathways and phosphatidic acid as therapeutic targets in cancer.Pharmacological reviews · 2014Review
- Phospholipase D in cell signaling: from a myriad of cell functions to cancer growth and metastasis.The Journal of biological chemistry · 2014Review
- Phosphorylation of Rab5a protein by protein kinase Cϵ is crucial for T-cell migration.The Journal of biological chemistry · 2014Article
- Molecular mechanisms of N-formyl-methionyl-leucyl-phenylalanine-induced superoxide generation and degranulation in mouse neutrophils: phospholipase D is dispensable.Molecular and cellular biology · 2013Article
- Interplay between FAK, PKCδ, and p190RhoGAP in the regulation of endothelial barrier function.Microvascular research · 2012Review
- The exquisite regulation of PLD2 by a wealth of interacting proteins: S6K, Grb2, Sos, WASp and Rac2 (and a surprise discovery: PLD2 is a GEF).Cellular signalling · 2011Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Integrin signaling plays critical roles in cell adhesion, spreading, and migration, and it is generally accepted that to regulate these integrin functions accurately, localized actin remodeling is required. However, the molecular mechanisms that control the targeting of actin regulation molecules to the proper sites are unknown. We previously demonstrated that integrin-mediated cell spreading and migration on fibronectin are dependent on the localized activation of phospholipase D (PLD). However, the mechanism underlying PLD activation by integrin is largely unknown. Here we demonstrate that protein kinase Cδ (PKCδ) is required for integrin-mediated PLD signaling. After integrin stimulation, PKCδ is activated and translocated to the edges of lamellipodia, where it colocalizes with PLD2. The abrogation of PKCδ activity inhibited integrin-induced PLD activation and cell spreading. Finally, we show that Thr566 of PLD2 is directly phosphorylated by PKCδ and that PLD2 mutation in this region prevents PLD2 activation, PLD2 translocation to the edge of lamellipodia, Rac translocation, and cell spreading after integrin activation. Together, these results suggest that PKCδ is a primary regulator of integrin-mediated PLD activation via the direct phosphorylation of PLD, which is essential for directing integrin-induced cell spreading.
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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.