ArticleInternational journal of molecular sciences2020
C-Src is Activated by the EGF Receptor in a Pathway that Mediates JNK and ERK Activation by Gonadotropin-Releasing Hormone in COS7 Cells.
Article in International journal of molecular sciences, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 14 citations in OpenAlex.
- Blockade of the CCL2-CCR2 axis attenuates fibrosis and parasite load in vesicular echinococcosis by inhibiting the PI3K-AKT pathway that regulates angiogenesis and hepatic stellate cell apoptosis.Parasites & vectors · 2026Article
- Targeting the PI3K/AKT signaling pathway: an important molecular mechanism of herbal medicine in the treatment of MASLD/MASH.Frontiers in nutrition · 2025Review
- Targeting CCL2-CCR2 signaling pathway alleviates macrophage dysfunction in COPD via PI3K-AKT axis.Cell communication and signaling : CCS · 2024Article
- JNK Cascade-Induced Apoptosis-A Unique Role in GqPCR Signaling.International journal of molecular sciences · 2023Review
- MFI2 upregulation promotes malignant progression through EGF/FAK signaling in oral cavity squamous cell carcinoma.Cancer cell international · 2023Article
- GSPT1 Functions as a Tumor Promoter in Human Liver Cancer.Current medical science · 2023Article
- Overexpression of eRF3a Promotes Cell Proliferation and Migration in Liver Cancer.Current medical science · 2022Article
- New Structural Perspectives in G Protein-Coupled Receptor-Mediated Src Family Kinase Activation.International journal of molecular sciences · 2021Review
- GnRH-Related Neurohormones in the Fruit FlyInternational journal of molecular sciences · 2021Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
The key participants in G-protein-coupled receptor (GPCR) signaling are the mitogen-activated protein kinase (MAPK) signaling cascades. The mechanisms involved in the activation of the above cascades by GPCRs are not fully elucidated. The prototypical GPCR is the receptor for gonadotropin-releasing hormone (GnRHR), which serves as a key regulator of the reproductive system. Here, we expressed GnRHR in COS7 cells and found that GnRHR transmits its signals to MAPKs mainly via Gαi and the EGF receptor, without the involvement of Hb-EGF or PKCs. The main pathway that leads to JNK activation downstream of the EGF receptor involves a sequential activation of c-Src and PI3K. ERK activation by GnRHR is mediated by the EGF receptor, which activates Ras either directly or via c-Src. Beside the main pathway, the dissociated Gβγ and β-arrestin may initiate additional (albeit minor) pathways that lead to MAPK activation in the transfected COS7 cells. The pathways detected are significantly different from those in other GnRHR-bearing cells, indicating that GnRH can utilize various signaling mechanisms for MAPK activation. The unique pathway elucidated here, in which c-Src and PI3K are sequentially activated downstream of the EGF receptor, may serve as a prototype of signaling mechanisms by GnRHR and additional GPCRs in various cell types.
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