The Experts below are selected from a list of 282 Experts worldwide ranked by ideXlab platform
Walter Birchmeier - One of the best experts on this subject based on the ideXlab platform.
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mutation of juxtamembrane Tyrosine Residue 1001 suppresses loss of function mutations of the met receptor in epithelial cells
Proceedings of the National Academy of Sciences of the United States of America, 1995Co-Authors: K M Weidner, Martin Sachs, Dieter Riethmacher, Walter BirchmeierAbstract:Abstract Signals transduced by the met Tyrosine kinase, which is the receptor for scatter factor/hepatocyte growth factor, are of major importance for the regulation of epithelial cell motility, morphogenesis, and proliferation. We report here that different sets of Tyrosine Residues in the cytoplasmic domain of the met receptor affect signal transduction in epithelial cells in a positive or negative fashion: mutation of the C-terminal Tyrosine Residues 13-16 (Y1311, Y1347, Y1354, and Y1363) reduced or abolished ligand-induced cell motility and branching morphogenesis. In contrast, mutation of the juxtamembrane Tyrosine Residue 2 (Y1001) produced constitutively mobile, fibroblastoid cells. Furthermore, the gain-of-function mutation of Tyrosine Residue 2 suppressed the loss-of-function mutations of Tyrosine Residue 15 or 16. The opposite roles of the juxtamembrane and C-terminal Tyrosine Residues may explain the suggested dual function of the met receptor in both epithelial-mesenchymal interactions and tumor progression.
Kenji Izuhara - One of the best experts on this subject based on the ideXlab platform.
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characterization of il 4 and il 13 signals dependent on the human il 13 receptor α chain 1 redundancy of requirement of Tyrosine Residue for stat3 activation
International Immunology, 2000Co-Authors: Ritsuko Umeshitasuyama, Rie Sugimoto, Mina Akaiwa, Kazuhiko Arima, Bin Yu, Morimasa Wada, Michihiko Kuwano, Koichi Nakajima, Naotaka Hamasaki, Kenji IzuharaAbstract:IL-4 and IL-13 are pleiotropic cytokines whose biological activities overlap with each other. IL-13 receptor α chain 1 (IL-13Rα1) is necessary for binding to IL-13, and the heterodimer composed of IL-13Rα1 and IL-4R α chain transduces IL-13 and IL-4 signals; however, the functional mapping of the intracellular domain of IL-13Rα1 is not fully understood. In this study, we constructed wild and mutated types of human IL-13Rα1, and analyzed IL-4 and IL-13 signals using an IL-13Rα1transfected human B cell line. Expression of IL-13Rα1 evoked STAT3 activation by IL-4 and IL-13, and in stimulated human B cells, on which IL-13Rα1 was highly expressed, IL-4 and IL-13 induced STAT3 activation. Replacement of the two Tyrosine Residues completely abolished STAT3 activation, although replacing either Tyrosine Residue alone retained it. Furthermore, we found that the Box1 region and the C-terminal tail of IL-13Rα1 were critical for binding to Tyk2, and activation of Jak1, Tyk2, the insulin receptor substrate-1 and STAT6 respectively. These results suggest that STAT3 activation is involved with IL-4 and IL-13 signals in human B cells along with the activation of STAT6, and that there is a unique sequence in IL-13Rα1 to activate STAT3.
Masabumi Shibuya - One of the best experts on this subject based on the ideXlab platform.
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essential role of flk 1 vegf receptor 2 Tyrosine Residue 1173 in vasculogenesis in mice
Proceedings of the National Academy of Sciences of the United States of America, 2005Co-Authors: Yoshiko Sakurai, Kaori Ohgimoto, Yuki Kataoka, Nobuaki Yoshida, Masabumi ShibuyaAbstract:Flk-1 (human counterpart, KDR) Tyrosine kinase, which is one of the two VEGF receptors, is crucial for vascular development. Recently, we showed that, among Tyrosine Residues of KDR, Tyrosine Residues 1175 (Y1175, corresponding to Y1173 in murine Flk-1) and Y1214 (Y1212 in Flk-1) are autophosphorylated in response to VEGF, and that Y1175 is important for VEGF-dependent phospholipase Cγ/PKC/mitogen-activated protein kinase activation leading to DNA synthesis in cultured endothelial cells. However, the importance of these Tyrosine Residues in Flk-1/KDR in vivo is not yet known. To examine the role of these Flk-1 Tyrosine Residues in vivo, we generated knock-in mice substituting Y1173 and Y1212 of the Flk-1 gene with phenylalanine, respectively. As a result, Flk-11173F homozygous mice died between embryonic days 8.5 and 9.5 without any organized blood vessels or yolk sac blood islands, and hematopoietic progenitors were severely reduced, similar to the case of Flk-1 null mice. In contrast, Flk-11212F homozygous mice were viable and fertile. These results suggest that the signaling via Y1173 of Flk-1 is essential for endothelial and hematopoietic development during embryogenesis.
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a highly conserved Tyrosine Residue at codon 845 within the kinase domain is not required for the transforming activity of human epidermal growth factor receptor
Biochemical and Biophysical Research Communications, 1992Co-Authors: Noriko Gotoh, Arinobu Tojo, Masayuki Hino, Yoshio Yazaki, Masabumi ShibuyaAbstract:Epidermal growth factor receptor (EGF-R) is a widely expressed ligand-dependent Tyrosine kinase. The Tyrosine Residue at 845 in EGF-R corresponds to Y416 of vc-src kinase, which is highly conserved and functionally important in many Tyrosine kinases. To clarify the functional role of Y845, we constructed a mutant human EGF-R in which this Tyrosine was replaced with phenylalanine and transfected it to NIH3T3 cells. EGF-R F845 induced EGF-dependent cellular transformation and revealed Tyrosine-autophosphorylation of a 170kDa protein, and initiated DNA synthesis similar to the wild-type EGF-R. We conclude here that Y845 is dispensable in the above mentioned functions of EGF-R Tyrosine kinase.
Veronique Fafeur - One of the best experts on this subject based on the ideXlab platform.
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phosphorylation of the met receptor on juxtamembrane Tyrosine Residue 1001 inhibits its caspase dependent cleavage
Cellular Signalling, 2009Co-Authors: Julien Deheuninck, Gautier Goormachtigh, Benedicte Foveau, Zongling Ji, Catherine Leroy, Frederic Ancot, Vincent Villeret, David Tulasne, Veronique FafeurAbstract:The MET Tyrosine kinase is the hepatocyte growth factor/scatter factor (HGF/SF) receptor, which elicits multiple biological responses in epithelial cells, including cell survival. We previously demonstrated that in stress conditions, the MET receptor is cleaved by caspases within its juxtamembrane region, generating a pro-apoptotic intracellular fragment of 40 kDa. The caspase cleavage site at aspartic acid D1000 is adjacent to Tyrosine Y1001, which when phosphorylated upon MET activation, is involved in CBL recruitment, allowing receptor ubiquitination and down regulation. Scanning mutagenesis of the MET juxtamembrane region led us to demonstrate that V999 and D1000 are essential for the caspase cleavage, while D1000 and Y1001 are essential for CBL recruitment. By examining whether overlapping of these sites leads to a functional interference, an inverse relationship was found between generation of p40 MET and phosphorylation of MET, with a direct involvement of phosphorylated Y1001 in protecting MET against its caspase cleavage. A molecular modeling analysis of caspase 3 interaction with the juxtamembrane region of MET confirmed that phosphorylation of this Tyrosine is not compatible with its recognition by active caspase 3. These data demonstrate a direct protection mechanism of an activated phosphorylated MET receptor, against its caspase-dependent cleavage.
K M Weidner - One of the best experts on this subject based on the ideXlab platform.
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mutation of juxtamembrane Tyrosine Residue 1001 suppresses loss of function mutations of the met receptor in epithelial cells
Proceedings of the National Academy of Sciences of the United States of America, 1995Co-Authors: K M Weidner, Martin Sachs, Dieter Riethmacher, Walter BirchmeierAbstract:Abstract Signals transduced by the met Tyrosine kinase, which is the receptor for scatter factor/hepatocyte growth factor, are of major importance for the regulation of epithelial cell motility, morphogenesis, and proliferation. We report here that different sets of Tyrosine Residues in the cytoplasmic domain of the met receptor affect signal transduction in epithelial cells in a positive or negative fashion: mutation of the C-terminal Tyrosine Residues 13-16 (Y1311, Y1347, Y1354, and Y1363) reduced or abolished ligand-induced cell motility and branching morphogenesis. In contrast, mutation of the juxtamembrane Tyrosine Residue 2 (Y1001) produced constitutively mobile, fibroblastoid cells. Furthermore, the gain-of-function mutation of Tyrosine Residue 2 suppressed the loss-of-function mutations of Tyrosine Residue 15 or 16. The opposite roles of the juxtamembrane and C-terminal Tyrosine Residues may explain the suggested dual function of the met receptor in both epithelial-mesenchymal interactions and tumor progression.
