Publications by authors named "J Overvoorde"

Article Synopsis
  • Noonan syndrome (NS) is an autosomal dominant disorder linked to mutations in the PTPN11 gene, leading to symptoms such as congenital heart disease, short stature, and distinct facial features.
  • Interestingly, patients with LEOPARD syndrome (LS) have inactivating mutations in the same gene but display similar symptoms, highlighting the complexity of Shp2 signaling.
  • The study identifies "protein zero-related" (PZR) as a key protein involved in NS and LS, with its abnormal phosphorylation promoting symptoms by enhancing Shp2 activity and affecting cell migration during zebrafish gastrulation.
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The PTPN11 (protein-tyrosine phosphatase, non-receptor type 11) gene encodes SHP2, a cytoplasmic PTP that is essential for vertebrate development. Mutations in PTPN11 are associated with Noonan and LEOPARD syndrome. Human patients with these autosomal dominant disorders display various symptoms, including short stature, craniofacial defects and heart abnormalities.

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A versatile assay for protein tyrosine phosphatases (PTP) employing 3-nitrophosphotyrosine containing peptidic substrates is described. These therapeutically important phosphatases feature in signal transduction pathways. The assay involves spectrophotometric detection of 3-nitrotyrosine production from 3-nitrophosphotyrosine containing peptidic substrates, which are accepted by many PTPs.

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Phosphatases and kinases regulate the crucial phosphorylation post-translational modification. In spite of their similarly important role in many diseases and therapeutic potential, phosphatases have received arguably less attention. One reason for this is a scarcity of high-throughput phosphatase assays.

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Over the last two decades the zebrafish has emerged as a powerful model organism in science. The experimental accessibility, the broad range of zebrafish mutants, and the highly conserved genetic and biochemical pathways between zebrafish and mammals lifted zebrafish to become one of the most attractive vertebrate models to study gene function and to model human diseases. Zebrafish cell lines are highly attractive to investigate cell biology and zebrafish cell lines complement the experimental tools that are available already.

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