Focal adhesion kinase (FAK), MAP kinases and the nuclear transcription factor Elk-1 have been reported to be implicated in the same cellular processes, however, their direct or indirect interaction and potential function(s) has not been documented. Here, we explored the association of FAK with Elk-1, the implication of Elk-1 in the regulation of FAK and MAP kinases expression as well as apoptosis, in HK-2 cells. Biochemical and immunofluorescence approaches strongly support the association of low molecular weight protein bands, recognized by FAK antibodies, with Elk-1 or p(ser383)Elk-1. The FAK/Elk-1 complex is found, mainly, in the cytoplasm, near the nuclear membrane periphery, raising the possibility that Elk-1 may have alternative extranuclear function(s) in HK-2 cells. Furthermore, we demonstrated that Elk-1 siRNA-mediated knockdown experiments, increased apoptosis. By contrast, Elk-1 siRNA decreased significantly the expression of FAK and MAP kinases, supporting the hypothesis that Elk-1 may act as a potential physiological substrate and regulator of FAK and MAP kinases expression. These results strongly support that Elk-1 protein is a novel binding-protein partner for FAK, a finding that significantly broadens the potential functioning of FAK and Elk-1.
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http://dx.doi.org/10.1002/jcp.21390 | DOI Listing |
The Rac1 P29S hotspot mutation in cutaneous melanoma is associated with resistance to MAPK pathway inhibitors (MAPKi) and worse clinical outcomes. Moreover, activation of Rac1 guanine exchange factors (GEFs) also promotes MAPKi-resistance, particularly in undifferentiated melanoma cells. Here we delineate mechanisms of Rac1-driven MAPKi-resistance and identify strategies to inhibit the growth of this class of cutaneous melanomas.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2025
Department of Marine Biology, Charney School of Marine Sciences, University of Haifa, Haifa 3498838, Israel.
Biomineralization is the utilization of different minerals by a vast array of organisms to form hard tissues and shape them in various forms. Within this diversity, a common feature of all mineralized tissues is their high stiffness, implying that mechanosensing could be commonly used in biomineralization. Yet, the role of mechanosensing in biomineralization is far from clear.
View Article and Find Full Text PDFBiochem Pharmacol
December 2024
The National Clinical Research Center for Kidney Diseases, Nanjing Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China; The State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, China. Electronic address:
Podocyte injury leads to proteinuria and glomerular diseases. Different podocyte injuries have distinct mechanisms. It is desirable to use a regimen that targets the mechanism of a given podocyte injury for a specific and improved result.
View Article and Find Full Text PDFEur J Pharmacol
December 2024
Department of Pharmacology, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, 410078, Hunan, China; Hunan Provincial Key Laboratory of Cardiovascular Research, Central South University, Changsha, 410078, Hunan, China. Electronic address:
Aortic aneurysm and dissection pose fatal threats but no effective drug therapies are available. Previous work has been directed to reduce risk factors or target key pathological events, but none of the translational efforts succeeds. Here, we attempt to repurpose dimethyl fumarate (DMF), an FDA-approved immunomodulatory drug for multiple sclerosis, for the treatment of aortic aneurysm and dissection.
View Article and Find Full Text PDFFront Immunol
November 2024
Regeneron Pharmaceuticals Inc., Tarrytown, NY, United States.
Background: Development of anti-drug antibodies (ADAs) and neutralizing antibodies (NAbs) to monoclonal antibodies may adversely impact pharmacokinetics, efficacy, and/or safety.
Objective: To describe incidence, titer, and persistence of dupilumab ADAs and NAbs, and their effects on pharmacokinetics, efficacy, and safety in patients with atopic dermatitis (AD).
Methods: This analysis included seven phase 3 randomized, placebo-controlled (N=2,992) and two long-term open-label extension (N=2,287) trials of subcutaneous dupilumab in adults and pediatric patients with moderate-to-severe AD.
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