EurekaMag.com logo
+ Site Statistics
References:
53,869,633
Abstracts:
29,686,251
+ Search Articles
+ Subscribe to Site Feeds
EurekaMag Most Shared ContentMost Shared
EurekaMag PDF Full Text ContentPDF Full Text
+ PDF Full Text
Request PDF Full TextRequest PDF Full Text
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter
Follow on LinkedInFollow on LinkedIn

+ Translate

RAS signaling pathway mutations and hypertrophic cardiomyopathy: getting into and out of the thick of it



RAS signaling pathway mutations and hypertrophic cardiomyopathy: getting into and out of the thick of it



Journal of Clinical Investigation 121(3): 844-847



In this issue of the JCI, Wu et al. and Marin et al. describe two new mouse models of inherited disorders of the RAS/MAPK signal transduction pathway that display hypertrophic cardiomyopathy (HCM); the model from the former paper was from a gain-of-function Raf1 mutation, and the model from the latter paper was from a protein tyrosine phosphatase, non-receptor type 11 (Ptpn11) mutated allele encoding Shp2 with impaired catalytic function. The two groups show that HCM arises from increased signaling through Erk1/2 and the mTor complex 1, respectively, and that those cardiac issues can be prevented or reversed with small-molecule therapies inhibiting the appropriate pathway. Aside from being the first studies of treatment for Noonan syndrome and related disorders in a mammalian system, these papers provide important insights into the role of RAS signaling in cardiac hypertrophy and suggest the complexity in developing meaningful therapy for individuals with these RASopathies.

(PDF emailed within 0-6 h: $19.90)

Accession: 055333409

Download citation: RISBibTeXText

PMID: 21339640

DOI: 10.1172/JCI46399



Related references

Gene-specific increase in the energetic cost of contraction in hypertrophic cardiomyopathy caused by thick filament mutations. Cardiovascular Research 103(2): 248-257, 2015

Point mutations in human b cardiac myosin heavy chain have differential effects on sarcomeric structure and assembly: an ATP binding site change disrupts both thick and thin filaments, whereas hypertrophic cardiomyopathy mutations display normal assembly. The Journal of Cell Biology 137(1): 1-40, 1997

Point Mutations in Human β Cardiac Myosin Heavy Chain Have Differential Effects on Sarcomeric Structure and Assembly: An ATP Binding Site Change Disrupts Both Thick and Thin Filaments, Whereas Hypertrophic Cardiomyopathy Mutations Display Normal Assembly. Journal of Cell Biology 137(1): 131-140, 1997

Point mutations in human beta cardiac myosin heavy chain have differential effects on sarcomeric structure and assembly: an ATP binding site change disrupts both thick and thin filaments, whereas hypertrophic cardiomyopathy mutations display normal assembly. Journal of Cell Biology 137(1): 131-140, 1997

Coexistence of Digenic Mutations in Both Thin (TPM1) and Thick (MYH7) Filaments of Sarcomeric Genes Leads to Severe Hypertrophic Cardiomyopathy in a South Indian FHCM. Dna and Cell Biology 34(5): 350-359, 2015

Analysis of 8 sarcomeric candidate genes for feline hypertrophic cardiomyopathy mutations in cats with hypertrophic cardiomyopathy. Journal of Veterinary Internal Medicine 23(4): 840-843, 2009

Hypertrophic cardiomyopathy in Noonan Syndrome closely mimics familial hypertrophic cardiomyopathy due to sarcomeric mutations. International Journal of Cardiovascular Imaging 22(3-4): 493-495, 2005

Hypertrophic cardiomyopathy: Two homozygous cases with typical hypertrophic cardiomyopathy and three new mutations in cases with progression to dilated cardiomyopathy. Biochemical & Biophysical Research Communications 309(2): 391-398, September 19, 2003

Hypertrophic cardiomyopathy mutations increase myofilament Ca2+ buffering, alter intracellular Ca2+ handling, and stimulate Ca2+-dependent signaling. Journal of Biological Chemistry 293(27): 10487-10499, 2018

Familial hypertrophic cardiomyopathy (FHC) medicine: The cloning and study of two novel mutations in the regulatory light chain (RLC) of myosin that cause familial hypertrophic cardiomyopathy (FHC). Ethnicity and Disease 15(3, Suppl. 4): 111-112, 2005

Mutations in COX15 produce a defect in the mitochondrial heme biosynthetic pathway, causing early-onset fatal hypertrophic cardiomyopathy. American Journal of Human Genetics 72(1): 101-114, 2002

Prevalence of sequence variants in the RAS-mitogen activated protein kinase signaling pathway in pre-adolescent children with hypertrophic cardiomyopathy. Circulation. Cardiovascular Genetics 5(3): 317-326, 2012

The 50-year history, controversy, and clinical implications of left ventricular outflow tract obstruction in hypertrophic cardiomyopathy from idiopathic hypertrophic subaortic stenosis to hypertrophic cardiomyopathy: from idiopathic hypertrophic subaortic stenosis to hypertrophic cardiomyopathy. Journal of the American College of Cardiology 54(3): 191-200, 2009

Outcome of clinical versus genetic family screening in hypertrophic cardiomyopathy with focus on cardiac beta-myosin gene mutations: prediction of clinical status--is molecular genetics a new tool for the management of hypertrophic cardiomyopathy in clinical practice?. Cardiovascular Research 57(2): 298-301, 2003

Early changes in apical rotation in genotype positive children with hypertrophic cardiomyopathy mutations without hypertrophic changes on two-dimensional imaging. Journal of the American Society of Echocardiography 27(2): 215-221, 2014