ArticleMolecular biology of the cell2009
Phosphatidylinositol-4-phosphate 5-kinase 1alpha mediates extracellular calcium-induced keratinocyte differentiation.
Article in Molecular biology of the cell, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 60 citations in OpenAlex.
- Implicates of PIP5K1α in asthma-related biological processes: insights into mechanisms and therapeutic potential.Journal of translational medicine · 2025Review
- Various Cellular Components and Its Signaling Cascades Through the Involvement of Signaling Messengers in Keratinocyte Differentiation.Antioxidants (Basel, Switzerland) · 2025Review
- A phosphatidylinositol phosphate kinase inhibits Ras activation and regulates chemorepulsion in Dictyostelium discoideum.Journal of cell science · 2023Article
- Role of vitamin D and calcium signaling in epidermal wound healing.Journal of endocrinological investigation · 2023Review
- p120-catenin suppresses proliferation and tumor growth of oral squamous cell carcinoma via inhibiting nuclear phospholipase C-γ1 signaling.Journal of cellular physiology · 2020Article
- Vitamin D and calcium signaling in epidermal stem cells and their regeneration.World journal of stem cells · 2020Review
- New aspects of vitamin D metabolism and action - addressing the skin as source and target.Nature reviews. Endocrinology · 2020Review
- PIP4Ks Suppress Insulin Signaling through a Catalytic-Independent Mechanism.Cell reports · 2019Article
- Calcium-Sensing Receptor Regulates Epidermal Intracellular CaThe Journal of investigative dermatology · 2019Article
- p120-Catenin Is Required for Dietary Calcium Suppression of Oral Carcinogenesis in Mice.Journal of cellular physiology · 2017Article
- Phospholipase Cδ1 regulates p38 MAPK activity and skin barrier integrity.Cell death and differentiation · 2017Article
- Combined Deletion of the Vitamin D Receptor and Calcium-Sensing Receptor Delays Wound Re-epithelialization.Endocrinology · 2017Article
- HPV8-E6 Interferes with Syntenin-2 Expression through Deregulation of Differentiation, Methylation and Phosphatidylinositide-Kinase Dependent Mechanisms.Frontiers in microbiology · 2017Article
- ISA-2011B, a Phosphatidylinositol 4-Phosphate 5-Kinase α Inhibitor, Impairs CD28-Dependent Costimulatory and Pro-inflammatory Signals in Human T Lymphocytes.Frontiers in immunology · 2017Article
- Control of diverse subcellular processes by a single multi-functional lipid phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2].The Biochemical journal · 2016Review
- Phosphatidylinositol 4-Phosphate 5-Kinases in the Regulation of T Cell Activation.Frontiers in immunology · 2016Review
- IQGAP1 is a phosphoinositide effector and kinase scaffold.Advances in biological regulation · 2016Review
- Phosphoprotein Phosphatase 1 Is Required for Extracellular Calcium-Induced Keratinocyte Differentiation.BioMed research international · 2016Article
- Disruption of Vitamin D and Calcium Signaling in Keratinocytes Predisposes to Skin Cancer.Frontiers in physiology · 2016Review
- In serum, higher parathyroid hormone but not lower vitamin D is associated with oral squamous cell carcinoma.Current oncology (Toronto, Ont.) · 2015Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Extracellular calcium (Cao) is a major regulator of keratinocyte differentiation, but the mechanism is unclear. Phosphatidylinositol-4-phosphate 5-kinase 1alpha (PIP5K1alpha) is critical in synthesizing phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2]. In this study, we sought to determine whether PIP5K1alpha plays a role in mediating the ability of Cao to induce keratinocyte differentiation. We found that treatment of human keratinocytes in culture with Cao resulted in increased PIP5K1alpha level and activity, as well as PI(4,5)P2 level, binding of phosphatidylinositol 3,4,5-triphosphate [PI(3,4,5)P3] to and activation of phospholipase C-gamma1 (PLC-gamma1), with the resultant increase in inositol 1,4,5-trisphosphate (IP3) and intracellular calcium (Cai). Knockdown of PIP5K1alpha in human keratinocytes blocked Cao-induced increases in the binding of PI(3,4,5)P3 to PLC-gamma1; PLC-gamma1 activity; levels of PI(4,5)P2, IP3, and Cai; and induction of keratinocyte differentiation markers. Coimmunoprecipitation and confocal studies revealed that Cao stimulated PIP5K1alpha recruitment to the E-cadherin-catenin complex in the plasma membrane. Knockdown of E-cadherin or beta-catenin blocked Cao-induced activation of PIP5K1alpha. These results indicate that after Cao stimulation PIP5K1alpha is recruited by the E-cadherin-catenin complex to the plasma membrane where it provides the substrate PI(4,5)P2 for both PI3K and PLC-gamma1. This signaling pathway is critical for Cao-induced generation of the second messengers IP3 and Cai and keratinocyte differentiation.
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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.