AI Article Synopsis

  • PDGF-BB binds to its receptors, activating several signaling pathways crucial for cell survival and growth, particularly in mesenchymal cells.
  • Erk5 MAP kinase activation in smooth muscle cells is regulated by various proteins including Mekk2, Mek1/2, and PKC, illustrating the interplay between Erk1/2 and Erk5 pathways.
  • Although Erk5 does not accumulate in the nucleus upon PDGF-BB stimulation, it is essential for Smad1/5/8 signaling, which is mediated through bone morphogenetic proteins (BMPs), indicating its role in gene expression regulation in the cytoplasm.

Article Abstract

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.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cellsig.2016.06.013DOI Listing

Publication Analysis

Top Keywords

map kinase
12
erk5
10
platelet-derived growth
8
activation erk5
8
dependent mekk2
8
mekk2 mek1/2
8
kinase pathways
8
erk5 map
8
response pdgf-bb
8
erk5 activation
8

Similar Publications

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 PDF

MAP Kinase Signaling at the Crossroads of Inflammasome Activation.

Immunol 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 PDF

Shh Protects the Injured Spinal Cord in Mice by Promoting the Proliferation and Inhibiting the Apoptosis of Nerve Cells via the Gli1-TGF-β1/ERK Axis.

Cell 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 PDF

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 PDF

Basic Science and Pathogenesis.

Alzheimers 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.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!