ArticleJournal of human genetics2005
Functional analysis of PTPN11/SHP-2 mutants identified in Noonan syndrome and childhood leukemia.
Article in Journal of human genetics, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
What it found
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Who cites it
54 citing papers in PubMed, 131 citations in OpenAlex.
- Large-scale whole-genome sequencing reveals the landscape and health implications of de novo mutations.Nature medicine · 2026Article
- High-throughput biochemical phenotyping of SHP2 variants reveals the molecular basis of diseases and allosteric drug inhibition.bioRxiv : the preprint server for biology · 2026Article
- Domain-specific phenotypic profiles in RAF1-related Noonan syndrome.European journal of human genetics : EJHG · 2026Article
- Noonan Syndrome, Cancer Risk, and Growth Hormone TreatmentJournal of clinical research in pediatric endocrinology · 2025Review
- Article
- Gene signatures and genotype-phenotype correlations of sensorineural hearing loss in Noonan syndrome and related RASopathies.Scientific reports · 2025Article
- Article
- Recurrent Missense Driver STAT5BAnti-cancer agents in medicinal chemistry · 2025Article
- Update on Pediatric Cancer Surveillance Recommendations for Patients with Neurofibromatosis Type 1, Noonan Syndrome, CBL Syndrome, Costello Syndrome, and Related RASopathies.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Review
- Novel paediatric case of a spinal high-grade astrocytoma with piloid features in a patient with Noonan Syndrome.NPJ precision oncology · 2024Article
- The expression of congenital Shoc2 variants induces AKT-dependent crosstalk activation of the ERK1/2 pathway.Human molecular genetics · 2024Article
- Influences of RASopathies on Neuroanatomical Variation in Children.Biological psychiatry. Cognitive neuroscience and neuroimaging · 2024Article
- A microglia clonal inflammatory disorder in Alzheimer's Disease.bioRxiv : the preprint server for biology · 2024Article
- Ganglioglioma with adverse clinical outcome and atypical histopathological features were defined by alterations in PTPN11/KRAS/NF1 and other RAS-/MAP-Kinase pathway genes.Acta neuropathologica · 2023Article
- From Stem to Sternum: The Role of Shp2 in the Skeleton.Calcified tissue international · 2023Review
- SH2 Domains: Folding, Binding and Therapeutical Approaches.International journal of molecular sciences · 2022Review
- Article
- Mutation ofCancers · 2022Article
- Combination Approaches to Target PD-1 Signaling in Cancer.Frontiers in immunology · 2022Review
- Article
Corrections and comments
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Authors and funding
19 authors at 13 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Noonan syndrome (NS) is characterized by short stature, characteristic facial features, and heart defects. Recently, missense mutations of PTPN11, the gene encoding protein tyrosine phosphatase (PTP) SHP-2, were identified in patients with NS. Further, somatic mutations in PTPN11 were detected in childhood leukemia. Recent studies showed that the phosphatase activities of five mutations identified in NS and juvenile myelomonocytic leukemia (JMML) were increased. However, the functional properties of the other mutations remain unidentified. In this study, in order to clarify the differences between the mutations identified in NS and leukemia, we examined the phosphatase activity of 14 mutants of SHP-2. We identified nine mutations, including a novel F71I mutation, in 16 of 41 NS patients and two mutations, including a novel G503V mutation, in three of 29 patients with leukemia. Immune complex phosphatase assays of individual mutants transfected in COS7 cells showed that ten mutants identified in NS and four mutants in leukemia showed 1.4-fold to 12.7-fold increased activation compared with wild-type SHP-2. These results suggest that the pathogenesis of NS and leukemia is associated with enhanced phosphatase activity of mutant SHP-2. A comparison of the phosphatase activity in each mutant and a review of previously reported cases showed that high phosphatase activity observed in mutations at codons 61, 71, 72, and 76 was significantly associated with leukemogenesis.
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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.