ArticleScience advances2023
RAS-dependent RAF-MAPK hyperactivation by pathogenic RIT1 is a therapeutic target in Noonan syndrome-associated cardiac hypertrophy.
Article in Science advances, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 24 citations in OpenAlex.
- Clinical consensus guidelines for the management of Noonan syndrome in Japan.Clinical pediatric endocrinology : case reports and clinical investigations : official journal of the Japanese Society for Pediatric Endocrinology · 2026Article
- Article
- Atrial Septal Defect Surgical Closure Following Trametinib Utilization in Noonan Syndrome-Associated Hypertrophic Cardiomyopathy.JACC. Case reports · 2026Article
- Structure of SHOC2-KRAS-PP1C complex reveals RAS isoform-specific determinants and insights into targeting complex assembly by RAS inhibitors.Nature communications · 2026Article
- Neonatal Noonan syndrome with acute kidney injury and systemic capillary leak syndrome caused by aFrontiers in pediatrics · 2026Article
- Phenotypic Analysis of Embryos in a Noonan Syndrome Model Mouse With the Rit1 A57G Mutation.Molecular genetics & genomic medicine · 2025Article
- Ubiquitin-independent pathway regulates the RIT1-MAPK pathway in chordoma progression.Cell death & disease · 2025Article
- Guanine Nucleotide Exchange Factors and Small GTPases: Their Regulation and Functions, Diseases, and Therapeutic Targets.MedComm · 2025Review
- Structural basis for LZTR1 recognition of RAS GTPases for degradation.Science (New York, N.Y.) · 2025Article
- RIT1 Drives Oncogenic Transformation and Is an Actionable Target in Lung Adenocarcinoma.Cancer research · 2025Article
- RIT1 Promotes the Proliferation of Gliomas Through the Regulation of the PI3K/AKT/c-Myc Signalling Pathway.Journal of cellular and molecular medicine · 2025Article
- Dysregulation of RAS proteostasis by autosomal-dominant LZTR1 mutation induces Noonan syndrome-like phenotypes in mice.JCI insight · 2024Article
- Inhibition and degradation of NRAS with a pan-NRAS monobody.Oncogene · 2024Article
- Article
- Functional and structural insights into RAS effector proteins.Molecular cell · 2024Review
- Complex interplay between RAS GTPases and RASSF effectors regulates subcellular localization of YAP.EMBO reports · 2024Article
- Novel therapeutic perspectives in Noonan syndrome and RASopathies.European journal of pediatrics · 2024Review
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 1 country.
Funding
Abstract
RIT1 is a RAS guanosine triphosphatase (GTPase) that regulates different aspects of signal transduction and is mutated in lung cancer, leukemia, and in the germline of individuals with Noonan syndrome. Pathogenic RIT1 proteins promote mitogen-activated protein kinase (MAPK) hyperactivation; however, this mechanism remains poorly understood. Here, we show that RAF kinases are direct effectors of membrane-bound mutant RIT1 necessary for MAPK activation. We identify critical residues in RIT1 that facilitate interaction with membrane lipids and show that these are necessary for association with RAF kinases and MAPK activation. Although mutant RIT1 binds to RAF kinases directly, it fails to activate MAPK signaling in the absence of classical RAS proteins. Consistent with aberrant RAF/MAPK activation as a driver of disease, we show that pathway inhibition alleviates cardiac hypertrophy in a mouse model of
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