ArticleThe American journal of pathology2007
Focal adhesion kinase controls pH-dependent epidermal barrier homeostasis by regulating actin-directed Na+/H+ exchanger 1 plasma membrane localization.
Article in The American journal of pathology, 2007. 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, 27 citations in OpenAlex.
- Ophiobolin A derivatives with enhanced activities under tumor-relevant acidic conditions.Bioorganic & medicinal chemistry letters · 2024Article
- Neutrophil-Derived Reactive Oxygen Orchestrates Epithelial Cell Signaling Events during Intestinal Repair.The American journal of pathology · 2019Article
- In situ visualization of glucocerebrosidase in human skin tissue: zymography versus activity-based probe labeling.Journal of lipid research · 2017Article
- Induced Pluripotent Stem Cell Differentiation and Three-Dimensional Tissue Formation Attenuate Clonal Epigenetic Differences in Trichohyalin.Stem cells and development · 2016Article
- Endoplasmic Reticulum Calcium Regulates Epidermal Barrier Response and Desmosomal Structure.The Journal of investigative dermatology · 2016Review
- LeftyA decreases Actin Polymerization and Stiffness in Human Endometrial Cancer Cells.Scientific reports · 2016Article
- Prolactin Signaling Stimulates Invasion via Na(+)/H(+) Exchanger NHE1 in T47D Human Breast Cancer Cells.Molecular endocrinology (Baltimore, Md.) · 2016Article
- Altered epidermal lipid processing and calcium distribution in the KID syndrome mouse model Cx26S17F.FEBS letters · 2015Article
- 3D In vitro model of a functional epidermal permeability barrier from human embryonic stem cells and induced pluripotent stem cells.Stem cell reports · 2014Article
- sPLA2 and the epidermal barrier.Biochimica et biophysica acta · 2014Article
- pH sensing by FAK-His58 regulates focal adhesion remodeling.The Journal of cell biology · 2013Article
- Acidic extracellular microenvironment and cancer.Cancer cell international · 2013Article
- Trefoil factor 2 requires Na/H exchanger 2 activity to enhance mouse gastric epithelial repair.The Journal of biological chemistry · 2011Article
- Involvement of signaling molecules on na/h exchanger-1 activity in human monocytes.The open cardiovascular medicine journal · 2010Article
- Article
- Establishment of cell lines from mouse embryos with early embryonic lethality.Cell communication & adhesion · 2008Article
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 1 country.
Funding
Abstract
Ubiquitously expressed focal adhesion kinase (FAK), linked to multiple intracellular signaling pathways, has previously been shown to control cell motility, invasion, proliferation, and survival. Using mice with a keratinocyte-restricted deletion of fak (FAK(K5 KO)), we report here a novel role for FAK: maintenance of adult epidermal permeability barrier homeostasis. Abundant lacunae of unprocessed lipids in stratum corneum (SC) of FAK(K5 KO) mice and delayed barrier recovery pointed to malfunction of pH-dependent enzymes active in extracellular space of SC. Measuring the SC pH gradient showed significantly more neutral pH values in FAK(K5 KO) mice, suggesting the importance of FAK for acidification. Moreover, normal functions were restored when FAK(K5 KO) mice were exposed to a surface pH typical of mouse SC (pH = 5.5). Baseline levels and response to barrier disruption of secretory phospholipase A2 isoforms, enzymes that mediate generation of free fatty acids in epidermis, appeared similar in both FAK(K5 KO) and control littermates. We found that the critical SC acidification regulator Na(+)/H(+) exchanger 1 failed to localize to the plasma membrane in FAK-deficient keratinocytes both in vivo and in vitro. Thus, for plasma membrane localization in terminally differentiated keratinocytes, Na(+)/H(+) exchanger 1 requires an intact actin cytoskeleton, which is impaired in FAK-deficient cells.
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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.