ArticleScientific reports2016
SCF/c-kit transactivates CXCR4-serine 339 phosphorylation through G protein-coupled receptor kinase 6 and regulates cardiac stem cell migration.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 24 citations in OpenAlex.
- Stimulatory Effects of Mesenchymal Stem Cells on cKit+ Cardiac Stem Cells Are Mediated by SDF1/CXCR4 and SCF/cKit Signaling Pathways.Circulation research · 2016Trial
- Imatinib mesylate promotes melanogenesis through the modulation of p38 and MITF in murine cells.Toxicological research · 2025Article
- Combined effects of pioglitazone and doxorubicin on migration and invasion of MDA-MB-231 breast cancer cells.Journal of the Egyptian National Cancer Institute · 2022Article
- c-MYB- and PGC1a-dependent metabolic switch induced by MYBBP1A loss in renal cancer.Molecular oncology · 2019Article
- Review
- GRK2 mediates TCR-induced transactivation of CXCR4 and TCR-CXCR4 complex formation that drives PI3Kγ/PREX1 signaling and T cell cytokine secretion.The Journal of biological chemistry · 2018Article
- Hypoxia-stressed cardiomyocytes promote early cardiac differentiation of cardiac stem cells through HIF-1Acta pharmaceutica Sinica. B · 2018Article
- TCR-CXCR4 signaling stabilizes cytokine mRNA transcripts via a PREX1-Rac1 pathway: implications for CTCL.Blood · 2017Article
- G Protein-Coupled Receptor Kinases in the Inflammatory Response and Signaling.Advances in immunology · 2017Review
- Improving nelarabine efficacy in T cell acute lymphoblastic leukemia by targeting aberrant PI3K/AKT/mTOR signaling pathway.Journal of hematology & oncology · 2016Article
- Mesenchymal Stem Cells Drive Cardiac Stem Cell Chemotaxis, Proliferation, and Phenotype via CXCR4 and cKit Signaling.Circulation research · 2016Article
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
C-kit positive cardiac stem cells (CSCs) have been shown to contribute to myocardial regeneration after infarction. Previously, we have shown that the c-kit ligand stem cell factor (SCF) can induce CSC migration into the infarcted area during myocardial infarction (MI). However, the precise mechanism involved is not fully understood. In this study, we found that CSCs also express C-X-C chemokine receptor type 4 (CXCR4), which is a typical member of the seven transmembrane-spanning G protein-coupled receptor (GPCR). In vitro, activation of c-kit signalling by SCF promotes migration of CSCs with increased phosphorylation of CXCR4-serine 339, p38 mitogen-activated protein kinase (p38 MAPK) and extracellular regulated protein kinases 1/2 (ERK1/2). Knockdown of CXCR4 expression by siRNA reduces SCF/c-kit-induced migration and downstream signalling. As previously reported, CXCR4-serine 339 phosphorylation is mainly regulated by GPCR kinase 6 (GRK6); thus, silencing of GRK6 expression by siRNA impairs CXCR4-serine 339 phosphorylation and migration of CSCs caused by SCF. In vivo, knockdown of GRK6 impairs the ability of CSCs to migrate into peri-infarcted areas. These results demonstrate that SCF-induced CSC migration is regulated by the transactivation of CXCR4-serine 339 phosphorylation, which is mediated by GRK6.
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