Platelet-derived growth factor-BB (PDGF-BB) binds to its tyrosine kinase receptors (PDGFRs) and stimulates mitogenicity and survival of cells of mesenchymal origin. Activation of PDGFRs initiates a number of downstream signaling pathways, including phosphatidyl 3'-inositol kinase (PI3-kinase), phospholipase Cγ and MAP kinase pathways. In this report, we show that Erk5 MAP kinase is activated in response to PDGF-BB in the smooth muscle cell line MOVAS in a manner dependent on Mekk2, Mek1/2, Mek5, PI3-kinase and protein kinase C (PKC). The co-operation of Mek1/2 and Mekk2 in the activation of Erk5, suggests a close co-regulation between the Erk1/2 and Erk5 MAP kinase pathways. Furthermore, we found that classical PKCs are important for Erk5 activation. In addition, we found that PKCζ interacts with Erk5 and may exert a negative feed-back effect. We observed no nuclear accumulation of Erk5 in response to PDGF-BB stimulation, however, we identified a mechanism by which cytoplasmic Erk5 influences gene expression; Erk5 was essential for PDGF-BB-mediated Smad1/5/8 signaling by stimulating release and/or activation of bone morphogenetic protein(s) (BMPs). Thus, PDGF-BB-induced Erk5 activation involves parallel stimulatory and inhibitory pathways and promotes Smad1/5/8 signaling.
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http://dx.doi.org/10.1016/j.cellsig.2016.06.013 | DOI Listing |
Sci Total Environ
January 2025
Department of Environmental Science and Engineering, Fudan University, Shanghai, PR China.
The outbreak of cyanobacterial blooms poses an increasingly serious ecological challenge. Our previous study found that calcium peroxide (CaO) has a high inhibitory effect on cyanobacteria, along with a practical application potential in cyanobacteria-dominated lakes. In order to explore the sensitivity of aquatic ecosystems to CaO treatment, we conducted this study to elucidate the ecological impact of CaO on Vallisneria natans (V.
View Article and Find Full Text PDFImmunol Rev
January 2025
Department of Internal Medicine and Paediatrics, Ghent University, Ghent, Belgium.
Inflammasomes are crucial mediators of both antimicrobial host defense and inflammatory pathology, requiring stringent regulation at multiple levels. This review explores the pivotal role of mitogen-activated protein kinase (MAPK) signaling in modulating inflammasome activation through various regulatory mechanisms. We detail recent advances in understanding MAPK-mediated regulation of NLRP3 inflammasome priming, licensing and activation, with emphasis on MAPK-induced activator protein-1 (AP-1) signaling in NLRP3 priming, ERK1 and JNK in NLRP3 licensing, and TAK1 in connecting death receptor signaling to NLRP3 inflammasome activation.
View Article and Find Full Text PDFCell Biochem Funct
January 2025
Stem Cells & Biotherapy Engineering Research Center of Henan, College of Life Science and Technology, Xinxiang Medical University, Xinxiang, China.
Spinal cord injury (SCI) is a common neurological trauma that cannot be completely cured with surgical techniques and medications. In this study, we established a mouse SCI model and used an adeno-associated virus (AAV) to achieve the high expression of sonic hedgehog (Shh) at the injury site to further investigate the therapeutic effect and mechanism of Shh on SCI. The results of the present study show that Shh may promote motor function recovery.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Georgia Institute of Technology, Atlanta, GA, USA.
Background: Mitogen activated protein kinase (MAPK) signaling is a critical regulator of microglial phenotype, including phagocytic function, cytokine expression, and motility, among others. Importantly, both canonical and non-canonical MAPK signaling is directly activated by RTKs, including Interestingly, CSF1R, is activated by two agonists, CSF1 and IL-34, which have been shown to activate the receptor in different ways that can lead to However, little is known about how the affect microglial MAPK signaling, and whether their effects are dependent on disease state/Aβ exposure. In this study, we hypothesized that IL-34 and CSF-1 elicit distinct patterns of MAPK signaling activation in microglia and MAPK activation would be dependent on whether the cells were exposed to Aβ.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
CSIR-CFTRI, Mysore, Karnataka, India.
Background: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by senile plaques, amyloid-beta (Aβ), and neuroinflammation. The key targets in the treatment of AD are inhibiting the production of amyloid-beta (Aβ), sphingomyelinase, and inflammation. Among the mechanisms, sphingolipids (specifically Ceramides) are recognized as distinctive mediators associated with the pathology of AD.
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