scholarly journals Holes in the Plasma Membrane Mimic Torso-Like Perforin in Torso Tyrosine Kinase Receptor Activation in the Drosophila Embryo

Genetics ◽  
2018 ◽  
Vol 210 (1) ◽  
pp. 257-262 ◽  
Author(s):  
Alessandro Mineo ◽  
Esther Fuentes ◽  
Marc Furriols ◽  
Jordi Casanova
Keyword(s):  
Plasma Membrane ◽  
Tyrosine Kinase ◽  
Receptor Activation ◽  
Drosophila Embryo ◽  
Tyrosine Kinase Receptor

scholarly journals Revising Endosomal Trafficking under Insulin Receptor Activation

2021 ◽  
Vol 22 (13) ◽  
pp. 6978
Author(s):  
Maria J. Iraburu ◽  
Tommy Garner ◽  
Cristina Montiel-Duarte
Keyword(s):  
Plasma Membrane ◽  
Tyrosine Kinase ◽  
Insulin Receptor ◽  
Molecular Mechanisms ◽  
Receptor Activation ◽  
Small Gtpases ◽  
Early Endosome ◽  
Tyrosine Kinase Receptors ◽  
Endosomal Trafficking ◽  
Cell Functions

The endocytosis of ligand-bound receptors and their eventual recycling to the plasma membrane (PM) are processes that have an influence on signalling activity and therefore on many cell functions, including migration and proliferation. Like other tyrosine kinase receptors (TKR), the insulin receptor (INSR) has been shown to be endocytosed by clathrin-dependent and -independent mechanisms. Once at the early endosome (EE), the sorting of the receptor, either to the late endosome (LE) for degradation or back to the PM through slow or fast recycling pathways, will determine the intensity and duration of insulin effects. Both the endocytic and the endosomic pathways are regulated by many proteins, the Arf and Rab families of small GTPases being some of the most relevant. Here, we argue for a specific role for the slow recycling route, whilst we review the main molecular mechanisms involved in INSR endocytosis, sorting and recycling, as well as their possible role in cell functions.

scholarly journals The product of a gas6 splice variant allows the release of the domain responsible for Axl tyrosine kinase receptor activation

FEBS Letters ◽  
1997 ◽  
Vol 415 (1) ◽  
pp. 59-63 ◽  
Author(s):  
Sandro Goruppi ◽  
Harvey Yamane ◽  
Paolo Marcandalli ◽  
Andy Garcia ◽  
Cris Clogston ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Splice Variant ◽  
Receptor Activation ◽  
Tyrosine Kinase Receptor

scholarly journals The spatial control of Torso RTK activation: a C-terminal fragment of the Trunk protein acts as a signal for Torso receptor in the Drosophila embryo

Development ◽  
2001 ◽  
Vol 128 (9) ◽  
pp. 1709-1715 ◽  
Author(s):  
A. Casali ◽  
J. Casanova
Keyword(s):  
Tyrosine Kinases ◽  
Receptor Tyrosine Kinases ◽  
Receptor Activation ◽  
Proteolytic Processing ◽  
Drosophila Embryo ◽  
Tyrosine Kinase Receptor ◽  
Spatial Control ◽  
Essential Step ◽  
Local Restriction ◽  
Carboxy Terminal

Regulated activation of receptor tyrosine kinases depends on both the presence of the receptors at the cell surface and on the availability of their ligands. In Drosophila, the torso tyrosine kinase receptor is distributed along the surface of the embryo but it is only activated at the poles by a diffusible extracellular ligand generated at each pole that is trapped by the receptor, thereby impeding further diffusion. Although it is known that this signal depends on the activity of several genes, such as torso-like and trunk, it is still unclear how is generated. The identification of the signal responsible for the torso receptor activation is an essential step towards understanding the mechanism that regulates the local restriction of torso signalling. Here we report that a fragment containing the carboxy-terminal 108 amino acids of the trunk protein retains trunk activity and is sufficient to activate torso signalling. We also show that this fragment bypasses the requirements for the other genes involved in the activation of the torso receptor. These results suggest that a cleaved form of the trunk protein acts as a signal for the torso receptor. We therefore propose that the restricted activation of the torso receptor is defined by the spatial control of the proteolytic processing of the trunk protein.

scholarly journals Sch proteins are localized on endoplasmic reticulum membranes and are redistributed after tyrosine kinase receptor activation.

1996 ◽  
Vol 16 (5) ◽  
pp. 1946-1954 ◽  
Author(s):  
L V Lotti ◽  
L Lanfrancone ◽  
E Migliaccio ◽  
C Zompetta ◽  
G Pelicci ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Plasma Membrane ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Tyrosine Kinase ◽  
Rough Endoplasmic Reticulum ◽  
Receptor Tyrosine Kinase ◽  
Receptor Activation ◽  
Kinase Activation ◽  
Epidermal Growth

The intracellular localization of Shc proteins was analyzed by immunofluorescence and immunoelectron microscopy in normal cells and cells expressing the epidermal growth factor receptor or the EGFR/erbB2 chimera. In unstimulated cells, the immunolabeling was localized in the central perinuclear area of the cell and mostly associated with the cytosolic side of rough endoplasmic reticulum membranes. Upon epidermal growth factor treatment and receptor tyrosine kinase activation, the immunolabeling became peripheral and was found to be associated with the cytosolic surface of the plasma membrane and endocytic structures, such as coated pits and endosomes, and with the peripheral cytosol. Receptor activation in cells expressing phosphorylation-defective mutants of Shc and erbB-2 kinase showed that receptor autophosphorylation, but not Shc phosphorylation, is required for redistribution of Shc proteins. The rough endoplasmic reticulum localization of Shc proteins in unstimulated cells and their massive recruitment to the plasma membrane, endocytic structures, and peripheral cytosol following receptor tyrosine kinase activation could account for multiple putative functions of the adaptor protein.

scholarly journals Differential receptor tyrosine kinase phosphorylation in the uterus of rats following developmental exposure to tetrabromobisphenol A

2021 ◽  
Vol 5 ◽  
pp. 239784732110471
Author(s):  
Lysandra Castro ◽  
Jingli Liu ◽  
Linda Yu ◽  
Alanna D Burwell ◽  
Trey O Saddler ◽  
...  
Keyword(s):  
Growth Factor ◽  
Tyrosine Kinase ◽  
Receptor Tyrosine Kinase ◽  
Early Life ◽  
Endometrial Adenocarcinoma ◽  
Growth Factor Receptor ◽  
Receptor Activation ◽  
Tetrabromobisphenol A ◽  
Tyrosine Kinase Receptor ◽  
Uterine Tumors

Tetrabromobisphenol A (TBBPA) is a brominated flame retardant that induces endometrial adenocarcinoma and other uterine tumors in Wistar Han rats; however, early molecular events or biomarkers of TBBPA exposure remain unknown. We investigated the effects of TBBPA on growth factor receptor activation [phospho-receptor tyrosine kinases (RTKs)] in uteri of rats following early-life exposures. Pregnant Wistar Han rats were exposed to TBBPA (0, 0.1, 25, and 250 mg/kg bw/day) via oral gavage on gestation day 6 through weaning of pups on postnatal day (PND) 21. Pups were exposed in utero, through lactation, and by daily gavage from PND 22 to PND 90. Uterine horns were collected (at PND 21, PND 33, and PND 90) and formalin-fixed or frozen for histologic, immunohistochemical, phospho-RTK arrays, or western blot analysis. At PND 21, the phospho-RTKs, fibroblast growth factor receptor 2 and 3 (FGFR2 and FGFR3), neurotrophic tyrosine kinase receptor type 3 (TRKC), and EPH receptor A1 (EPHA1) were significantly increased at different treatment concentrations. Several phospho-RTKs were also significantly overexpressed at PND 33 which included epithelial growth factor receptor (EGFR), FGFR2, FGFR3, FGFR4, insulin-like growth factor receptor 1 (IGF1R), insulin receptor (INSR), AXL receptor tyrosine kinase (AXL), MER proto-oncogene, tyrosine kinase (MERTK), platelet derived growth factor receptor alpha and beta (PDGFRA and PDGFRB), ret proto-oncogene (RET), tyrosine kinase with immunoglobulin-like and EGF-like domains 1 and 2 (TIE1 and TIE2), TRKA, kinase insert domain receptor (KDR;VEGFR2), fms related receptor tyrosine kinase (FLT4; VEGFR3), and EPHA1 at different treatment concentrations. EGFR, a RTK overexpressed in endometrial cancer in women, remained significantly increased for all treatment groups at PND 90. Erb-B2 receptor tyrosine kinase 2 (ERBB2) and IGF1R were overexpressed at PND 33 and remained increased through PND 90, although ERBB2 was statistically significant at PND 90. The phospho-RTKs, FGFR3, AXL, TYRO3 protien tyrosine kinase (TYRO3; DTK), HGFR, TRKC, FLT1/VEGFR1, and EPHB2 and 4 were also statistically significant at PND 90 at different treatment doses. The downstream effector, phospho-MAPK44/42, was also increased in uteri of treated rats. Our findings show RTKs are dysregulated following early-life TBBPA exposures and their sustained activation may contribute to TBBPA-induced uterine tumors observed in rats later in life.

Pattern formation under the control of the terminal system in the Drosophila embryo

Development ◽  
1990 ◽  
Vol 110 (2) ◽  
pp. 621-628 ◽  
Author(s):  
J. Casanova
Keyword(s):  
Pattern Formation ◽  
Tyrosine Kinase ◽  
Protein A ◽  
Primary Response ◽  
The Body ◽  
Drosophila Embryo ◽  
Tyrosine Kinase Receptor ◽  
Terminal System ◽  
Gap Genes

The specification of the most anterior and posterior domains of the Drosophila embryo depends on the activity of the torso protein, a putative tyrosine kinase receptor. Localized torso activity at the poles of the embryo generates graded information that specifies distinct portions of the body. The primary response to the terminal signal in the posterior end of the embryo is likely to be the activation of the gap genes huckebein and tailless. Here I address the question of how the graded maternal signal generates different elements of the pattern at the posterior end of the embryo and what role huckebein and tailless activities may play in this process. These experiments show that distinctly localized activities of huckebein and tailless are responsible for the appropriate expression of other genes known to be under the control of the terminal system. Moreover, they suggest that different elements of the terminal pattern can be specified in response to distinct levels of graded tailless activity.

scholarly journals Stable interaction between α5β1 integrin and Tie2 tyrosine kinase receptor regulates endothelial cell response to Ang-1

2005 ◽  
Vol 170 (6) ◽  
pp. 993-1004 ◽  
Author(s):  
Ilaria Cascone ◽  
Lucia Napione ◽  
Fabrizio Maniero ◽  
Guido Serini ◽  
Federico Bussolino
Keyword(s):  
Tyrosine Kinase ◽  
Cross Talk ◽  
Receptor Activation ◽  
Tyrosine Kinase Receptor ◽  
Dynamic Interactions ◽  
Tie2 Receptor ◽  
Low Concentrations ◽  
Endothelial Cell Response ◽  
Blocking Antibodies

During angiogenic remodeling, Ang-1, the ligand of Tie2 tyrosine kinase, is involved in vessel sprouting and stabilization through unclear effects on nascent capillaries and mural cells. In our study, we hypothesized that the Ang-1/Tie2 system could cross-talk with integrins, and be influenced by the dynamic interactions between extracellular matrix and endothelial cells (ECs). Here, we show that α5β1 specifically sensitizes and modulates Tie2 receptor activation and signaling, allowing EC survival at low concentrations of Ang-1 and inducing persistent EC motility. Tie2 and α5β1 interact constitutively; α5β1 binding to fibronectin increases this association, whereas Ang-1 stimulation recruits p85 and FAK to this complex. Furthermore, we demonstrate that Ang-1 is able to mediate selectively α5β1 outside-in FAK phosphorylation. Thus, Ang-1 triggers signaling pathways through Tie2 and α5β1 receptors that could cross-talk when Tie2/α5β1 interaction occurs in ECs plated on fibronectin. By using blocking antibodies, we consistently found that α5β1, but not αvβ3 activation, is essential to Ang-1–dependent angiogenesis in vivo.

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