ArticleDevelopment (Cambridge, England)2012
SHP-2 acts via ROCK to regulate the cardiac actin cytoskeleton.
Article in Development (Cambridge, England), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
20 citing papers in PubMed, 32 citations in OpenAlex.
- Targeting the CD47-SIRPα Axis in Atherosclerosis: From Pathogenesis to Therapeutic Implications.Journal of inflammation research · 2026Review
- Biomarker Landscape in RASopathies.International journal of molecular sciences · 2024Review
- Rho-Associated Protein Kinase Activity Is Required for Tissue Homeostasis in theJournal of developmental biology · 2024Article
- Hyperactivation of MEK1 in cortical glutamatergic neurons results in projection axon deficits and aberrant motor learning.Disease models & mechanisms · 2024Article
- PTPN11 Gene Mutations and Its Association with the Risk of Congenital Heart Disease.Disease markers · 2022Article
- Modeling (not so) rare developmental disorders associated with mutations in the protein-tyrosine phosphatase SHP2.Frontiers in cell and developmental biology · 2022Review
- Swimming toward solutions: Using fish and frogs as models for understanding RASopathies.Birth defects research · 2020Review
- Loss of Asb2 Impairs Cardiomyocyte Differentiation and Leads to Congenital Double Outlet Right Ventricle.iScience · 2020Article
- The Noonan Syndrome-linked Raf1L613V mutation drives increased glial number in the mouse cortex and enhanced learning.PLoS genetics · 2019Article
- RIT1 controls actin dynamics via complex formation with RAC1/CDC42 and PAK1.PLoS genetics · 2018Article
- Expanding the genetic toolkit in Xenopus: Approaches and opportunities for human disease modeling.Developmental biology · 2017Review
- Developmental SHP2 dysfunction underlies cardiac hypertrophy in Noonan syndrome with multiple lentigines.The Journal of clinical investigation · 2016Article
- The Lhx9-integrin pathway is essential for positioning of the proepicardial organ.Development (Cambridge, England) · 2016Article
- RASopathies: unraveling mechanisms with animal models.Disease models & mechanisms · 2015Review
- Elevated Ca2+ transients and increased myofibrillar power generation cause cardiac hypercontractility in a model of Noonan syndrome with multiple lentigines.American journal of physiology. Heart and circulatory physiology · 2015Article
- The role of the protein tyrosine phosphatase SHP2 in cardiac development and disease.Seminars in cell & developmental biology · 2015Review
- Congenital heart disease protein 5 associates with CASZ1 to maintain myocardial tissue integrity.Development (Cambridge, England) · 2014Article
- Cellular and molecular mechanisms underlying blood vessel lumen formation.BioEssays : news and reviews in molecular, cellular and developmental biology · 2014Review
- Tcf21 regulates the specification and maturation of proepicardial cells.Development (Cambridge, England) · 2013Article
- ROCKs cause SHP-wrecks and broken hearts.Small GTPasesArticle
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Noonan syndrome is one of the most common causes of human congenital heart disease and is frequently associated with missense mutations in the protein phosphatase SHP-2. Interestingly, patients with acute myelogenous leukemia (AML), acute lymphoblastic leukemia (ALL), juvenile myelomonocytic leukemia (JMML) and LEOPARD syndrome frequently carry a second, somatically introduced subset of missense mutations in SHP-2. To determine the cellular and molecular mechanisms by which SHP-2 regulates heart development and, thus, understand how Noonan-associated mutations affect cardiogenesis, we introduced SHP-2 encoding the most prevalent Noonan syndrome and JMML mutations into Xenopus embryos. Resulting embryos show a direct relationship between a Noonan SHP-2 mutation and its ability to cause cardiac defects in Xenopus; embryos expressing Noonan SHP-2 mutations exhibit morphologically abnormal hearts, whereas those expressing an SHP-2 JMML-associated mutation do not. Our studies indicate that the cardiac defects associated with the introduction of the Noonan-associated SHP-2 mutations are coupled with a delay or arrest of the cardiac cell cycle in M-phase and a failure of cardiomyocyte progenitors to incorporate into the developing heart. We show that these defects are a result of an underlying malformation in the formation and polarity of cardiac actin fibers and F-actin deposition. We show that these defects can be rescued in culture and in embryos through the inhibition of the Rho-associated, coiled-coil-containing protein kinase 1 (ROCK), thus demonstrating a direct relationship between SHP-2(N308D) and ROCK activation in the developing heart.
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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.