ArticleCellular signalling2015
RhoA Kinase (Rock) and p90 Ribosomal S6 Kinase (p90Rsk) phosphorylation of the sodium hydrogen exchanger (NHE1) is required for lysophosphatidic acid-induced transport, cytoskeletal organization and migration.
Article in Cellular signalling, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 23 citations in OpenAlex.
- NHE1 in Gastrointestinal Inflammation and Cancer: A Double-Edged Regulator.Digestive diseases and sciences · 2026Review
- A system-wide investigation into the phosphoregulatory network of TNIK and its cellular implications.Frontiers in bioinformatics · 2026Article
- Identifying a Role for the Sodium Hydrogen Exchanger Isoform 1 in Idiopathic Pulmonary Fibrosis: A Potential Strategy to Modulate Profibrotic Pathways.Biomedicines · 2025Article
- A web portal for exploring kinase-substrate interactions.NPJ systems biology and applications · 2024Article
- Regulation of proton partitioning in kinase-activating acute myeloid leukemia and its therapeutic implication.Leukemia · 2022Article
- Sodium hydrogen exchanger (NHE1) palmitoylation and potential functional regulation.Life sciences · 2022Article
- Dynamic NaeLife · 2021Article
- Suppressing the NaCell death & disease · 2019Article
- Overcoming transporter-mediated multidrug resistance in cancer: failures and achievements of the last decades.Drug delivery and translational research · 2019Review
- The level of ROCK1 and ROCK2 in patients with pulmonary hypertension in plateau area.Scientific reports · 2018Article
- Rho kinase and NaPhysiological reports · 2018Article
- The Rho-associated kinase inhibitors Y27632 and fasudil promote microglial migration in the spinal cord via the ERK signaling pathway.Neural regeneration research · 2018Article
- The cleaved FAS ligand activates the Na(+)/H(+) exchanger NHE1 through Akt/ROCK1 to stimulate cell motility.Scientific reports · 2016Article
- Na+/H+ exchanger NHE1 regulation modulates metastatic potential and epithelial-mesenchymal transition of triple-negative breast cancer cells.Oncotarget · 2016Article
- Role of Rho kinase and Na+/H+ exchange in hypoxia-induced pulmonary arterial smooth muscle cell proliferation and migration.Physiological reports · 2016Article
- Clematichinenoside Serves as a Neuroprotective Agent Against Ischemic Stroke: The Synergistic Action of ERK1/2 and cPKC Pathways.Frontiers in cellular neuroscience · 2015Article
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11 authors at 3 institutions in 1 country.
Funding
Abstract
The sodium hydrogen exchanger isoform one (NHE1) plays a critical role coordinating asymmetric events at the leading edge of migrating cells and is regulated by a number of phosphorylation events influencing both the ion transport and cytoskeletal anchoring required for directed migration. Lysophosphatidic acid (LPA) activation of RhoA kinase (Rock) and the Ras-ERK growth factor pathway induces cytoskeletal reorganization, activates NHE1 and induces an increase in cell motility. We report that both Rock I and II stoichiometrically phosphorylate NHE1 at threonine 653 in vitro using mass spectrometry and reconstituted kinase assays. In fibroblasts expressing NHE1 alanine mutants for either Rock (T653A) or ribosomal S6 kinase (Rsk; S703A) we show that each site is partially responsible for the LPA-induced increase in transport activity while NHE1 phosphorylation by either Rock or Rsk at their respective site is sufficient for LPA stimulated stress fiber formation and migration. Furthermore, mutation of either T653 or S703 leads to a higher basal pH level and a significantly higher proliferation rate. Our results identify the direct phosphorylation of NHE1 by Rock and suggest that both RhoA and Ras pathways mediate NHE1-dependent ion transport and migration in fibroblasts.
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