ArticleThe Journal of biological chemistry2008
Noonan syndrome-associated SHP-2/Ptpn11 mutants enhance SIRPalpha and PZR tyrosyl phosphorylation and promote adhesion-mediated ERK activation.
Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 43 citations in OpenAlex.
- Clinical phenotypes and cochlear implant outcomes in patients with PTPN11-associated noonan spectrum disorders: Insights from a genetically screened cohort.European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery · 2026Article
- Mechanisms, functions and therapeutic targeting of protein tyrosine phosphatases.Nature reviews. Molecular cell biology · 2026Review
- SHP2 genetic variants in NSML-associated RASopathies disrupt the PZR-IRX transcription factor signaling axis.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- RNA-Seq Analysis Reveals Altered Expression of Cell Adhesion-Related Genes Following PZR Knockout in Lung Cancer Cells.Applied biochemistry and biotechnology · 2024Article
- Acute myeloid leukemia cells adhere to bone marrow and acquire chemoresistance by downregulating UNC5B expression.Frontiers in oncology · 2024Article
- Deciphering the molecular landscape: integrating single-cell transcriptomics to unravel myofibroblast dynamics and therapeutic targets in clear cell renal cell carcinomas.Frontiers in immunology · 2024Article
- Article
- Low-dose Dasatinib Ameliorates Hypertrophic Cardiomyopathy in Noonan Syndrome with Multiple Lentigines.Cardiovascular drugs and therapy · 2022Article
- Integrated in silico MS-based phosphoproteomics and network enrichment analysis of RASopathy proteins.Orphanet journal of rare diseases · 2021Article
- Drosophila RASopathy models identify disease subtype differences and biomarkers of drug efficacy.iScience · 2021Article
- Tyrosyl phosphorylation of PZR promotes hypertrophic cardiomyopathy in PTPN11-associated Noonan syndrome with multiple lentigines.JCI insight · 2020Article
- PCells · 2020Article
- Long Non-Coding RNA SPRY4-IT1 Reverses Cisplatin Resistance by Downregulating MPZL-1 via Suppressing EMT in NSCLC.OncoTargets and therapy · 2020Article
- MPZL1 is highly expressed in advanced gallbladder carcinoma and promotes the aggressive behavior of human gallbladder carcinoma GBC‑SD cells.Molecular medicine reports · 2019Article
- An endogenous retroviral envelope syncytin and its cognate receptor identified in the viviparous placentalProceedings of the National Academy of Sciences of the United States of America · 2017Article
- MPZL1 forms a signalling complex with GRB2 adaptor and PTPN11 phosphatase in HER2-positive breast cancer cells.Scientific reports · 2017Article
- Chromosomal contacts connect loci associated with autism, BMI and head circumference phenotypes.Molecular psychiatry · 2017Article
- SH2 Domain-Containing Phosphatase-2 Is a Novel Antifibrotic Regulator in Pulmonary Fibrosis.American journal of respiratory and critical care medicine · 2017Article
- Low-dose dasatinib rescues cardiac function in Noonan syndrome.JCI insight · 2016Article
- The extracellular interactome of the human adenovirus family reveals diverse strategies for immunomodulation.Nature communications · 2016Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Noonan syndrome (NS) is an autosomal dominant disorder that is associated with multiple developmental abnormalities. Activated mutations of the protein-tyrosine phosphatase, SHP-2/PTPN11, have been reported in approximately 50% of NS cases. Despite being activated, NS-associated SHP-2 mutants require plasma membrane proximity to evoke disease-associated signaling. Here we show that NS-associated SHP-2 mutants induce hypertyrosyl phosphorylation of the transmembrane glycoproteins, SIRPalpha (signal-regulatory protein alpha) and PZR (protein zero-related), resulting in their increased association with NS-associated SHP-2 mutants. NS-associated SHP-2 mutants enhanced SIRPalpha and PZR tyrosyl phosphorylation either by impairing SIRPalpha dephosphorylation or by promoting PZR tyrosyl phosphorylation. Importantly, during embryogenesis in a mouse model of NS, SIRPalpha and PZR were hypertyrosyl-phosphorylated and bound increased levels of the NS-associated SHP-2 mutant. SIRPalpha and PZR have been implicated in extracellular matrix-dependent signaling. Mouse embryonic fibroblasts derived from a mouse model of NS displayed enhanced ERK activation in response to fibronectin plating. Knockdown of SIRPalpha and PZR in these cells attenuated the enhanced activation of ERK following fibronectin plating. Thus, SIRPalpha and PZR serve as scaffolds that facilitate plasma membrane recruitment and signaling of NS-associated SHP-2 mutants.
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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.