ArticlePLoS genetics2018
RIT1 controls actin dynamics via complex formation with RAC1/CDC42 and PAK1.
Article in PLoS genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 38 citations in OpenAlex.
- Article
- Neonatal Noonan syndrome with acute kidney injury and systemic capillary leak syndrome caused by aFrontiers in pediatrics · 2026Article
- PAK1 Is Involved in Epileptogenesis by Regulating the Synaptic Plasticity of Hippocampal Neurons Through LIMK.Neurochemical research · 2025Article
- Article
- Modulating PAK1: Accessory Proteins as Promising Therapeutic Targets.Biomolecules · 2025Review
- Microtubule regulation in cancer cells.Frontiers in cell and developmental biology · 2025Article
- Rit1-TBC1D10B signaling modulates FcγR-mediated phagosome formation in RAW264 macrophages.Life science alliance · 2024Article
- Article
- A microglia clonal inflammatory disorder in Alzheimer's Disease.bioRxiv : the preprint server for biology · 2024Article
- RAS-dependent RAF-MAPK hyperactivation by pathogenic RIT1 is a therapeutic target in Noonan syndrome-associated cardiac hypertrophy.Science advances · 2023Article
- Beyond Pattern Recognition: TLR2 Promotes Chemotaxis, Cell Adhesion, and Migration in THP-1 Cells.Cells · 2023Article
- Review
- Cross-species analysis of LZTR1 loss-of-function mutants demonstrates dependency to RIT1 orthologs.eLife · 2022Article
- RhoGEF Trio Regulates Radial Migration of Projection Neurons via Its Distinct Domains.Neuroscience bulletin · 2022Article
- Noonan syndrome caused by RIT1 gene mutation: A case report and literature review.Frontiers in pediatrics · 2022Article
- The metastatic promoter DEPDC1B induces epithelial-mesenchymal transition and promotes prostate cancer cell proliferation via Rac1-PAK1 signaling.Clinical and translational medicine · 2020Article
- The molecular functions of RIT1 and its contribution to human disease.The Biochemical journal · 2020Review
- Mechanical Cues Affect Migration and Invasion of Cells From Three Different Directions.Frontiers in cell and developmental biology · 2020Review
- P21-Activated Kinase 1: Emerging biological functions and potential therapeutic targets in Cancer.Theranostics · 2020Review
- New Noonan syndrome model mice with RIT1 mutation exhibit cardiac hypertrophy and susceptibility to β-adrenergic stimulation-induced cardiac fibrosis.EBioMedicine · 2019Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
RIT1 belongs to the RAS family of small GTPases. Germline and somatic RIT1 mutations have been identified in Noonan syndrome (NS) and cancer, respectively. By using heterologous expression systems and purified recombinant proteins, we identified the p21-activated kinase 1 (PAK1) as novel direct effector of RIT1. We found RIT1 also to directly interact with the RHO GTPases CDC42 and RAC1, both of which are crucial regulators of actin dynamics upstream of PAK1. These interactions are independent of the guanine nucleotide bound to RIT1. Disease-causing RIT1 mutations enhance protein-protein interaction between RIT1 and PAK1, CDC42 or RAC1 and uncouple complex formation from serum and growth factors. We show that the RIT1-PAK1 complex regulates cytoskeletal rearrangements as expression of wild-type RIT1 and its mutant forms resulted in dissolution of stress fibers and reduction of mature paxillin-containing focal adhesions in COS7 cells. This effect was prevented by co-expression of RIT1 with dominant-negative CDC42 or RAC1 and kinase-dead PAK1. By using a transwell migration assay, we show that RIT1 wildtype and the disease-associated variants enhance cell motility. Our work demonstrates a new function for RIT1 in controlling actin dynamics via acting in a signaling module containing PAK1 and RAC1/CDC42, and highlights defects in cell adhesion and migration as possible disease mechanism underlying NS.
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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.