Frankfurt am Main, Germany
Frankfurt am Main, Germany

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Tomasovic A.,Justus Liebig University | Tomasovic A.,University Clinic of Frankfurt | Traub S.,University Clinic of Frankfurt | Tikkanen R.,Justus Liebig University | Tikkanen R.,University Clinic of Frankfurt
PLoS ONE | Year: 2012

Fibroblast growth factor receptor substrate 2 (FRS2α) is a signaling adaptor protein that regulates downstream signaling of many receptor tyrosine kinases. During signal transduction, FRS2 can be both tyrosine and threonine phosphorylated and forms signaling complexes with other adaptor proteins and tyrosine phosphatases. We have here identified flotillin-1 and the cbl-associated protein/ponsin (CAP) as novel interaction partners of FRS2. Flotillin-1 binds to the phosphotyrosine binding domain (PTB) of FRS2 and competes for the binding with the fibroblast growth factor receptor. Flotillin-1 knockdown results in increased Tyr phosphorylation of FRS2, in line with the inhibition of ERK activity in the absence of flotillin-1. CAP directly interacts with FRS2 by means of its sorbin homology (SoHo) domain, which has previously been shown to interact with flotillin-1. In addition, the third SH3 domain in CAP binds to FRS2. Due to the overlapping binding domains, CAP and flotillin-1 appear to compete for the binding to FRS2. Thus, our results reveal a novel signaling network containing FRS2, CAP and flotillin-1, whose successive interactions are most likely required to regulate receptor tyrosine kinase signaling, especially the mitogen activated protein kinase pathway. © 2012 Tomasovic et al.


Hecht T.,Goethe University Frankfurt | Brand J.,University Clinic of Frankfurt | Vlaho S.,University Clinic of Frankfurt
Journal of Pediatric Endocrinology and Metabolism | Year: 2012

We report on a 7-year-old girl with generalized seizures, somnolence, fever, and respiratory distress. The increase of sinus tachycardia with good hydration, sufficient analgesia, and hyperthermia in our patient led to the determination of thyroid hormones, and therefore finally to the diagnosis of a thyrotoxic crisis in Graves'disease. Thyrotoxic crisis is a very rare but severe disease with an incidence of 0.1/100,000- 3/100,000 among children. Important differential diagnoses of hyperthyroidism are Hashimoto thyroiditis, paraneoplastic thyroid-stimulating hormone production, thyroid autonomy, as well as central hyperthyroidism. Although symptoms disappear by thyrostatic therapy (thiamazole, carbimazole, dexamethasone), a euthyroid status could only be achieved by thyroidectomy. Thyrotoxic crisis should be considered a differential diagnosis in case of resistant unexplained sinus tachycardia, seizures, and encephalopathy. Immediate and adequate therapy contributes significantly to a reduction in the high morbidity and mortality rates. A combination of several treatment approaches for hyperthyroidism can lead to a successful outcome. © 2012 by Walter de Gruyter.

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