ArticleProceedings of the National Academy of Sciences of the United States of America2018
RSK2 drives cell motility by serine phosphorylation of LARG and activation of Rho GTPases.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 45 citations in OpenAlex.
- FAM65A, as a potential predictor of prognosis, promotes colorectal cancer progression via activating Ras/ERK/RSK signaling.iScience · 2026Article
- Discovery of a novel RSK2 inhibitor for the treatment of metastatic pancreatic cancer.Journal of enzyme inhibition and medicinal chemistry · 2025Article
- Integrative multi-omics and single-cell transcriptomics reveal ARHGEF12 driving chemoresistance in bladder cancer.Hereditas · 2025Article
- Guanine Nucleotide Exchange Factors and Small GTPases: Their Regulation and Functions, Diseases, and Therapeutic Targets.MedComm · 2025Review
- Drug Combinations Targeting FAK and MEK Overcomes Tumor Heterogeneity in Glioblastoma.Pharmaceutics · 2025Article
- Phosphoproteomics identifies determinants of PAK inhibitor sensitivity in leukaemia cells.Cell communication and signaling : CCS · 2025Article
- Article
- Targeting ARHGEF12 promotes neuroblastoma differentiation, MYCN degradation, and reduces tumorigenicity.Cellular oncology (Dordrecht, Netherlands) · 2023Article
- The role of RAS oncogenes in controlling epithelial mechanics.Trends in cell biology · 2023Review
- Dual thick and thin filament linked regulation of stretch- and L-NAME-induced tone in young and senescent murine basilar artery.Frontiers in physiology · 2023Article
- MLL regulates the actin cytoskeleton and cell migration by stabilising Rho GTPases via the expression of RhoGDI1.Journal of cell science · 2022Article
- The putative oncogenic role of WDTC1 in colorectal cancer.Carcinogenesis · 2022Article
- Regulation of Leukaemia Associated Rho GEF (LARG/ARHGEF12).Small GTPases · 2022Article
- RSK1 and RSK2 serine/threonine kinases regulate different transcription programs in cancer.Frontiers in cell and developmental biology · 2022Article
- Matriptase activation of Gq drives epithelial disruption and inflammation via RSK and DUOX.eLife · 2021Article
- The role of the p90 ribosomal S6 kinase family in prostate cancer progression and therapy resistance.Oncogene · 2021Review
- Dynamic Control of Signaling by Phosphorylation of PDZ Binding Motifs.Methods in molecular biology (Clifton, N.J.) · 2021Article
- ERK signalling: a master regulator of cell behaviour, life and fate.Nature reviews. Molecular cell biology · 2020Review
- Leukemia-Associated Rho Guanine Nucleotide Exchange Factor and Ras Homolog Family Member C Play a Role in Glioblastoma Cell Invasion and Resistance.The American journal of pathology · 2020Article
- ARHGEF12 regulates erythropoiesis and is involved in erythroid regeneration after chemotherapy in acute lymphoblastic leukemia patients.Haematologica · 2020Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Directed migration is essential for cell motility in many processes, including development and cancer cell invasion. RSKs (p90 ribosomal S6 kinases) have emerged as central regulators of cell migration; however, the mechanisms mediating RSK-dependent motility remain incompletely understood. We have identified a unique signaling mechanism by which RSK2 promotes cell motility through leukemia-associated RhoGEF (LARG)-dependent Rho GTPase activation. RSK2 directly interacts with LARG and nucleotide-bound Rho isoforms, but not Rac1 or Cdc42. We further show that epidermal growth factor or FBS stimulation induces association of endogenous RSK2 with LARG and LARG with RhoA. In response to these stimuli, RSK2 phosphorylates LARG at Ser1288 and thereby activates RhoA. Phosphorylation of RSK2 at threonine 577 is essential for activation of LARG-RhoA. Moreover, RSK2-mediated motility signaling depends on RhoA and -B, but not RhoC. These results establish a unique RSK2-dependent LARG-RhoA signaling module as a central organizer of directed cell migration and invasion.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.