scholarly journals FLT4 Mutations Are Associated with Segmental Lymphatic Dysfunction and Initial Lymphatic Aplasia in Patients with Milroy Disease

Genes ◽  
2021 ◽  
Vol 12 (10) ◽  
pp. 1611
Author(s):  
Ningfei Liu ◽  
Minzhe Gao
Keyword(s):  
Tyrosine Kinase ◽  
Protein Tyrosine Kinase ◽  
Clinical Signs ◽  
Lymphatic Vessels ◽  
Growth Factor Receptor ◽  
Kinase Domain ◽  
Tyrosine Kinase Domain ◽  
Missense Mutations ◽  
History Of ◽  
Endothelial Growth Factor

This study explored mutations in the Fms-related tyrosine kinase 4/vascular endothelial growth factor receptor 3 gene (FLT4) and lymphatic defects in patients with Milroy disease (MD). Twenty-nine patients with lower limb lymphedema were enrolled. Sixteen patients had a familial history of MD, while 13 patients exhibited sporadic MD. Clinical signs, FLT4 mutations, indocyanine green (ICG) lymphography findings, and skin tissue immunohistochemical staining results were evaluated. Twenty-eight variants in FLT4 were identified. Twelve of these have previously been reported, while 16 are novel. Of the 28 variants, 26 are missense mutations, and the remaining two comprise a splicing mutation and a non-frame shift mutation. Twenty-five variants are located in the intracellular protein tyrosine kinase domain; three are located in the extracellular immunoglobulin domain. Substantially delayed contrast-enhanced tortuous lymphatic vessels were visualized to the ankle or knee level in 15 of 23 patients who underwent ICG lymphography. No initial lymphatic vessels were visualized in skin specimens from four patients who did not exhibit lymphatic vessels during imaging analyses. No specific variant was identified in relation to the unique clinical phenotype. Segmental dysfunction of lymphatic vessels and initial lymphatic aplasia are present in MD patients with FLT4 mutations.

A recurrent mutation in the tyrosine kinase domain of fibroblast growth factor receptor 3 causes hypochondroplasia

1995 ◽  
Vol 10 (3) ◽  
pp. 357-359 ◽  
Author(s):  
Gary A. Bellus ◽  
Iain McIntosh ◽  
E. Anne Smith ◽  
Arthur S. Aylsworth ◽  
Ilkka Kaitila ◽  
...  
Keyword(s):  
Growth Factor ◽  
Tyrosine Kinase ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth Factor Receptor ◽  
Growth Factor Receptor ◽  
Kinase Domain ◽  
Recurrent Mutation ◽  
Tyrosine Kinase Domain ◽  
Fibroblast Growth

Functional dissection of p56lck, a protein tyrosine kinase which mediates interleukin-2-induced activation of the c-fos gene

1994 ◽  
Vol 14 (9) ◽  
pp. 5812-5819
Author(s):  
H Shibuya ◽  
K Kohu ◽  
K Yamada ◽  
E L Barsoumian ◽  
R M Perlmutter ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Tyrosine Kinases ◽  
Protein Tyrosine Kinase ◽  
Gene Activation ◽  
Interleukin 2 ◽  
Kinase Domain ◽  
Tyrosine Kinase Domain ◽  
Amino Acid Residues ◽  
Protein Tyrosine ◽  
Responsive Element

Members of the newly identified receptor family for cytokines characteristically lack the intrinsic protein tyrosine kinase domain that is a hallmark of other growth factor receptors. Instead, accumulating evidence suggests that these receptors utilize nonreceptor-type protein tyrosine kinases for downstream signal transduction by cytokines. We have shown previously that the interleukin-2 receptor beta-chain interacts both physically and functionally with a Src family member, p56lck, and that p56lck activation leads to induction of the c-fos gene. However, the mechanism linking p56lck activation with c-fos induction remains unelucidated. In the present study, we systematically examined the extent of c-fos promoter activation by expression of a series of p56lck mutants, using a transient cotransfection assay. The results define a set of the essential amino acid residues that regulate p56lck induction of the c-fos promoter. We also provide evidence that the serum-responsive element and sis-inducible element are both targets through which p56lck controls c-fos gene activation.

scholarly journals In VitroActivation and Inhibition of Recombinant EGFR Tyrosine Kinase Expressed inEscherichia coli

2013 ◽  
Vol 2013 ◽  
pp. 1-5 ◽  
Author(s):  
Jihene Elloumi-Mseddi ◽  
Karim Jellali ◽  
Sami Aifa
Keyword(s):  
Tyrosine Kinase ◽  
Kinase Activity ◽  
Growth Factor Receptor ◽  
Kinase Domain ◽  
Tyrosine Kinase Domain ◽  
Glutathione S Transferase ◽  
Amino Acid Peptide ◽  
Juxtamembrane Region ◽  
Exogenous Substrate ◽  
Epidermal Growth

The present work concerns the heterologous expression of the intracellular domain harbouring the tyrosine kinase activity of the epidermal growth factor receptor (EGFR). Protein expression was improved thanks to the deletion of a 13-amino acid peptide of the juxtamembrane region (JM). The recombinant proteins were produced as a glutathione S-transferase (GST) fusion inEscherichia coli, and the solubilisation was performed by sarkosyl addition during extraction. The produced proteins spontaneously dimerize allowing the activation of the tyrosine kinase domain in the presence of[γ-32P]ATP. The activity assay has revealed the autophosphorylation of EGFR proteins which was decreased in the presence of genistein. Our system could facilitate the screening of EGFR inhibitors without the need of adding an exogenous substrate.

scholarly journals Large-cell neuroendocrine carcinoma of lung with epidermal growth factor receptor (EGFR) gene mutation and co-expression of adenocarcinoma markers: a case report and review of the literature

2013 ◽  
Vol 8 ◽  
Author(s):  
Yasuhiro Sakai ◽  
Takashi Yamasaki ◽  
Yoshito Kusakabe ◽  
Daisuke Kasai ◽  
Yoshikazu Kotani ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Neuroendocrine Carcinoma ◽  
Growth Factor Receptor ◽  
Large Cell ◽  
Kinase Domain ◽  
Large Cell Neuroendocrine Carcinoma ◽  
Tyrosine Kinase Domain ◽  
High Grade ◽  
Epidermal Growth ◽  
L858r Mutation

Purpose: A high rate of response to treatment with epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) has been observed in certain patients (women, of East Asian ethnicity, with non-smoking history and adenocarcinoma histology) with mutations in exons 18 to 21 of the tyrosine kinase domain of EGFR. Some cases of high-grade neuroendocrine carcinoma of the lung harboring mutations have been sporadically reported. Methods: We describe the case of a 78-year-old woman with large-cell neuroendocrine carcinoma of the lung, with mutation in exon 21 L858R and co-expression of adenocarcinoma markers. Results: A mass (3.0 cm in diameter) was identified in the inferior lobe of the left lung, accompanied by metastases into ipsilateral mediastinal lymph nodes and elevations of serum pro-gastrin-releasing peptide and carcinoembryonic antigen. Initial transbronchial brushing cytology suggested high-grade neuroendocrine carcinoma favoring small-cell carcinoma in poorly smeared and degenerated preparations, and revealed exon 21 L858R mutation. Re-enlargement of the cancer and bone metastases was observed after chemotherapy, and further testing suggested large-cell neuroendocrine carcinoma with immunoreactivity to markers of primary lung adenocarcinoma and L858R mutation. High-grade neuroendocrine carcinoma with mutations in the tyrosine kinase domain of EGFR may be associated with adenocarcinoma, as reviewed from the literature and may also apply to our case. Conclusions: EGFR-TKI could provide better quality of life and survival in patients with advanced or relapsed high-grade neuroendocrine carcinoma with EGFR gene mutations. Further studies in this respect are warranted.

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