ArticleMolecular biology of the cell2005
Calcium-induced human keratinocyte differentiation requires src- and fyn-mediated phosphatidylinositol 3-kinase-dependent activation of phospholipase C-gamma1.
Article in Molecular biology of the cell, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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51 citing papers in PubMed, 97 citations in OpenAlex.
- Method and Analysis of High-Calcium Induced Differentiation of Human Primary KeratinocytesMethods and protocols · 2026Article
- A recurrent de novo damaging variant inProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Vitamin D in the Prevention and Treatment of Inflammatory Skin Diseases.International journal of molecular sciences · 2025Review
- Various Cellular Components and Its Signaling Cascades Through the Involvement of Signaling Messengers in Keratinocyte Differentiation.Antioxidants (Basel, Switzerland) · 2025Review
- Dysregulation of STS in keratinocytes promotes calcium signaling and differentiation.Scientific reports · 2025Article
- Effects of Th1/Th17 and Th2 cytokines on lipid metabolism in differentiated keratinocytes.Frontiers in physiology · 2025Article
- In vitro generation of epidermal keratinocytes from human CD34-positive hematopoietic stem cells.In vitro cellular & developmental biology. Animal · 2024Article
- Role of vitamin D and calcium signaling in epidermal wound healing.Journal of endocrinological investigation · 2023Review
- PepFect14 mediates the delivery of mRNA into human primary keratinocytes andFrontiers in pharmacology · 2023Article
- Generation of Keratinocytes from Human Induced Pluripotent Stem Cells Under Defined Culture Conditions.Cellular reprogramming · 2021Article
- Transcriptomic and Morphological Analysis of Cells Derived from Porcine Buccal Mucosa-Studies on an In Vitro Model.Animals : an open access journal from MDPI · 2020Article
- p120-catenin suppresses proliferation and tumor growth of oral squamous cell carcinoma via inhibiting nuclear phospholipase C-γ1 signaling.Journal of cellular physiology · 2020Article
- New aspects of vitamin D metabolism and action - addressing the skin as source and target.Nature reviews. Endocrinology · 2020Review
- Lung Endothelial Transcytosis.Comprehensive Physiology · 2020Review
- Keratinocyte differentiation promotes ER stress-dependent lysosome biogenesis.Cell death & disease · 2019Article
- Feeder Cells Free Rabbit Oral Mucosa Epithelial Cell Sheet Engineering.Tissue engineering and regenerative medicine · 2018Article
- Phosphoinositide 3-Kinase-Dependent Signalling Pathways in Cutaneous Squamous Cell Carcinomas.Cancers · 2017Review
- Combined Deletion of the Vitamin D Receptor and Calcium-Sensing Receptor Delays Wound Re-epithelialization.Endocrinology · 2017Article
- p120-Catenin Is Required for Dietary Calcium Suppression of Oral Carcinogenesis in Mice.Journal of cellular physiology · 2017Article
- Association of rs1801157 single nucleotide polymorphism of CXCL12 gene in breast cancer in Pakistan andPeerJ · 2017Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We have previously demonstrated that phospholipase C (PLC)-gamma1 is required for calcium-induced human keratinocyte differentiation. In the present study, we investigated whether the activation of PLC-gamma1 by nonreceptor kinases such as src and fyn plays a role in mediating this process. Our results showed that the combination of dominant negative src and fyn blocked calcium-stimulated PLC-gamma1 activity and human keratinocyte differentiation, whereas each separately has little effect. However, unlike the activation of PLC-gamma1 by epidermal growth factor, calcium-induced activation of PLC-gamma1 was not a result of direct tyrosine phosphorylation. Therefore, we examined an alternative mechanism, in particular phosphatidylinositol 3,4,5-triphosphate (PIP3) formed as a product of phosphatidylinositol 3-kinase (PI3K) activity. PIP3 binds to and activates PLC-gamma1. The combination of dominant negative src and fyn blocked calcium-induced tyrosine phosphorylation of the regulatory subunit of PI3K, p85alpha, and the activity of the catalytic subunit of PI3K. PI3K inhibitors blocked calcium activation of PLC-gamma1 as well as the induction of keratinocyte differentiation markers involucrin and transglutaminase. These data indicate that calcium activates PLC-gamma1 via increased PIP3 formation mediated by c-src- and fyn-activated PI3K. This activation is required for calcium-induced human keratinocyte differentiation.
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