Two FGF-receptor homologues of Drosophila: one is expressed in mesodermal primordium in early embryos

Development ◽  
1993 ◽  
Vol 117 (2) ◽  
pp. 751-761 ◽  
Author(s):  
E. Shishido ◽  
S. Higashijima ◽  
Y. Emori ◽  
K. Saigo
Keyword(s):  
Kinase Domain ◽  
Precursor Cells ◽  
Molecular Structures ◽  
Tyrosine Kinase Domain ◽  
Receptor System ◽  
Fgf Receptor ◽  
Extracellular Region ◽  
Early Embryos ◽  
Snail Proteins ◽  
Cns Midline

The fibroblast growth factor (FGF)/receptor system is thought to mediate various developmental events in vertebrates. We examined molecular structures and expression of DFR1 and DFR2, two Drosophila genes closely related to vertebrate FGF-receptor genes. DFR1 and DFR2 proteins contain two and five immunoglobulin-like domains, respectively, in the extracellular region, and a split tyrosine kinase domain in the intracellular region. In early embryos, DFR1 RNA expression, requiring both twist and snail proteins, is specific to mesodermal primordium and invaginated mesodermal cells. At later stages, putative muscle precursor cells and cells in the central nervous system (CNS) express DFR1. DFR2 expression occurs in endodermal precursor cells, CNS midline cells and certain ectodermal cells such as those of trachea and salivary duct. FGF-receptor homologues in Drosophila would thus appear essential for generation of mesodermal and endodermal layers, invaginations of various types of cells, and CNS formation.

scholarly journals Structure of the FGF Receptor Tyrosine Kinase Domain Reveals a Novel Autoinhibitory Mechanism

Cell ◽  
1996 ◽  
Vol 86 (4) ◽  
pp. 577-587 ◽  
Author(s):  
Moosa Mohammadi ◽  
Joseph Schlessinger ◽  
Stevan R Hubbard
Keyword(s):  
Tyrosine Kinase ◽  
Receptor Tyrosine Kinase ◽  
Kinase Domain ◽  
Tyrosine Kinase Domain ◽  
Fgf Receptor

scholarly journals Role of exon-16-deleted HER2 in breast carcinomas

2006 ◽  
Vol 13 (1) ◽  
pp. 221-232 ◽  
Author(s):  
F Castiglioni ◽  
E Tagliabue ◽  
M Campiglio ◽  
S M Pupa ◽  
A Balsari ◽  
...  
Keyword(s):  
Splice Variant ◽  
Kinase Domain ◽  
Critical Threshold ◽  
Tyrosine Kinase Domain ◽  
Her Family ◽  
Therapeutic Drugs ◽  
Extracellular Region ◽  
Her2 Mrna ◽  
Low Sensitivity

A splice variant of the human gene HER2, lacking exon-16 (ΔHER2) which encodes a small extracellular region, has been described. This altered receptor forms disulfide bond-stabilized homodimers. We report here that the ΔHER2 splice variant represents about 9% of the HER2 mRNA obtained from most of the 46 breast carcinoma samples with HER2 expression levels ranging from 3+ to 0 by HercepTest. Analysis of human cells transfected with ΔHER2 or wild-type (WT) cDNA revealed no growth of WT cells in nude mice, whereas clones expressing 10-fold less ΔHER2 were tumorigenic. Unlike WT transfectants, ΔHER2-expressing cells showed low sensitivity to two new therapeutic drugs targeting receptors of the HER family (ZD1839 and Trastuzumab), whereas an inhibitor of the HER2 tyrosine kinase domain (Emodin) blocked activation of both ΔHER2 and WT transfectants. Taken together, our findings indicate that the ΔHER2 transcript encodes the transforming form of the oncoprotein. It is plausible that malignant transformation arises when a critical threshold of ΔHER2 is reached in HER2-overexpressing tumors. Specific inhibitors of HER2 catalytic activity represent a promising approach to therapy of HER2-overexpressing tumors.

scholarly journals Elucidation of a four-site allosteric network in fibroblast growth factor receptor tyrosine kinases

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Huaibin Chen ◽  
William M Marsiglia ◽  
Min-Kyu Cho ◽  
Zhifeng Huang ◽  
Jingjing Deng ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Tyrosine Kinases ◽  
Functional Characterization ◽  
Growth Factor Receptor ◽  
Structural Similarity ◽  
Kinase Domain ◽  
Tyrosine Kinase Domain ◽  
Active Conformation ◽  
Long Distance ◽  
Fgf Receptor

Receptor tyrosine kinase (RTK) signaling is tightly regulated by protein allostery within the intracellular tyrosine kinase domains. Yet the molecular determinants of allosteric connectivity in tyrosine kinase domain are incompletely understood. By means of structural (X-ray and NMR) and functional characterization of pathogenic gain-of-function mutations affecting the FGF receptor (FGFR) tyrosine kinase domain, we elucidated a long-distance allosteric network composed of four interconnected sites termed the ‘molecular brake’, ‘DFG latch’, ‘A-loop plug’, and ‘αC tether’. The first three sites repress the kinase from adopting an active conformation, whereas the αC tether promotes the active conformation. The skewed design of this four-site allosteric network imposes tight autoinhibition and accounts for the incomplete mimicry of the activated conformation by pathogenic mutations targeting a single site. Based on the structural similarity shared among RTKs, we propose that this allosteric model for FGFR kinases is applicable to other RTKs.

NIDDM associated with mutation in tyrosine kinase domain of insulin receptor gene

Diabetes ◽  
1992 ◽  
Vol 41 (4) ◽  
pp. 521-526 ◽  
Author(s):  
S. Cocozza ◽  
A. Porcellini ◽  
G. Riccardi ◽  
A. Monticelli ◽  
G. Condorelli ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Insulin Receptor ◽  
Receptor Gene ◽  
Kinase Domain ◽  
Tyrosine Kinase Domain ◽  
Insulin Receptor Gene

scholarly journals Characterization of Atypical Protein Tyrosine Kinase (PTK) Genes and Their Role in Abiotic Stress Response in Rice

Plants ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 664
Author(s):  
Allimuthu Elangovan ◽  
Monika Dalal ◽  
Gopinathan Kumar Krishna ◽  
Sellathdurai Devika ◽  
Ranjeet Ranjan Kumar ◽  
...  
Keyword(s):  
Abiotic Stress ◽  
Stress Response ◽  
Tyrosine Kinase ◽  
Tyrosine Phosphorylation ◽  
Rice Genome ◽  
Kinase Domain ◽  
Tyrosine Kinase Domain ◽  
Protein Tyrosine ◽  
Dual Specificity ◽  
Submergence Stress

Tyrosine phosphorylation constitutes up to 5% of the total phophoproteome. However, only limited studies are available on protein tyrosine kinases (PTKs) that catalyze protein tyrosine phosphorylation in plants. In this study, domain analysis of the 27 annotated PTK genes in rice genome led to the identification of 18 PTKs with tyrosine kinase domain. The kinase domain of rice PTKs shared high homology with that of dual specificity kinase BRASSINOSTEROID-INSENSITIVE 1 (BRI1) of Arabidopsis. In phylogenetic analysis, rice PTKs clustered with receptor-like cytoplasmic kinases-VII (RLCKs-VII) of Arabidopsis. mRNAseq analysis using Genevestigator revealed that rice PTKs except PTK9 and PTK16 express at moderate to high level in most tissues. PTK16 expression was highly abundant in panicle at flowering stage. mRNAseq data analysis led to the identification of drought, heat, salt, and submergence stress regulated PTK genes in rice. PTK14 was upregulated under all stresses. qRT-PCR analysis also showed that all PTKs except PTK10 were significantly upregulated in root under osmotic stress. Tissue specificity and abiotic stress mediated differential regulation of PTKs suggest their potential role in development and stress response of rice. The candidate dual specificity PTKs identified in this study paves way for molecular analysis of tyrosine phosphorylation in rice.

scholarly journals Directed Discovery of Agents Targeting the Met Tyrosine Kinase Domain by Virtual Screening

2009 ◽  
Vol 52 (4) ◽  
pp. 943-951 ◽  
Author(s):  
Megan L. Peach ◽  
Nelly Tan ◽  
Sarah J. Choyke ◽  
Alessio Giubellino ◽  
Gagani Athauda ◽  
...  
Keyword(s):  
Virtual Screening ◽  
Tyrosine Kinase ◽  
Kinase Domain ◽  
Tyrosine Kinase Domain

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

Expanding the search for significant EGFR mutations in NSCLC outside of the tyrosine kinase domain with next-generation sequencing

2017 ◽  
Vol 34 (7) ◽  
Author(s):  
Matthew K. Stein ◽  
Lindsay Morris ◽  
Jennifer L. Sullivan ◽  
Moon Fenton ◽  
Ari VanderWalde ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Tyrosine Kinase ◽  
Kinase Domain ◽  
Egfr Mutations ◽  
Tyrosine Kinase Domain ◽  
Next Generation ◽  
Generation Sequencing
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