scholarly journals Germline MET pathogenic variants in papillary renal cell carcinomas type I: specific phenotype in French population and novel germline pathogenic variant MET c.3389T>C, p.(Leu1130Ser)

2021 ◽  
Author(s):  
Molka SEBAI ◽  
David TULASNE ◽  
Sandrine Caputo ◽  
Virginie VERKARRE ◽  
Marie FERNANDES ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Renal Cell ◽  
Kinase Domain ◽  
Pathogenic Variant ◽  
Renal Tumors ◽  
Tyrosine Kinase Domain ◽  
Functional Assay ◽  
Type I ◽  
Pathogenic Variants ◽  
Index Cases

Hereditary papillary renal cell carcinoma (HPRCC) is a rare inherited renal cancer syndrome characterized by bilateral and multifocal papillary type 1 renal tumors (PRCC1). Activating germline pathogenic variants of MET gene were identified in HPRCC families. We reviewed the medical and molecular records of a large French series of 158 patients screened for MET oncogenic variants (153 index-cases and five relatives). MET pathogenic variant rate was 10.4% (16/153) with 37.5% among patients with familial PRCC1 and 3.3% among patients with sporadic PRCC1 presentation. The phenotype in MET mutated cases was characteristic as PRCC1 tumors were mainly bilateral (82.3%) and multifocal (85.8%). Histologically, six out of seven patients with MET germline pathogenic variant harboured biphasic squamoid alveolar PRCC. Genetic screening identified in four index-cases a novel missense pathogenic variant within the tyrosine kinase domain: MET c.3389T>C, p.(Leu1130Ser). Functional assay confirmed its oncogenic effect with a constitutive phosphorylation of ERK protein and an abnormal focus formation induced. The genotype-phenotype correlation between MET pathogenic variants and PRCC1 presentation should encourage to widen the screening, especially toward non-familial PRCC1. This precise phenotype also constitutes a strong argument for the classification of novel missense variants within the tyrosine kinase domain when functional assays aren’t accessible.

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

scholarly journals Regulation of Jak2 Function by Phosphorylation of Tyr317 and Tyr637 during Cytokine Signaling

2009 ◽  
Vol 29 (12) ◽  
pp. 3367-3378 ◽  
Author(s):  
Scott A. Robertson ◽  
Rositsa I. Koleva ◽  
Lawrence S. Argetsinger ◽  
Christin Carter-Su ◽  
Jarrod A. Marto ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Kinase Activity ◽  
Feedback Inhibition ◽  
Dominant Role ◽  
Kinase Domain ◽  
Cytokine Signaling ◽  
Tyrosine Kinase Domain ◽  
Phosphorylation Sites ◽  
Cytokine Stimulation

ABSTRACT Jak2, the cognate tyrosine kinase for numerous cytokine receptors, undergoes multisite phosphorylation during cytokine stimulation. To understand the role of phosphorylation in Jak2 regulation, we used mass spectrometry to identify numerous Jak2 phosphorylation sites and characterize their significance for Jak2 function. Two sites outside of the tyrosine kinase domain, Tyr317 in the FERM domain and Tyr637 in the JH2 domain, exhibited strong regulation of Jak2 activity. Mutation of Tyr317 promotes increased Jak2 activity, and the phosphorylation of Tyr317 during cytokine signaling requires prior activation loop phosphorylation, which is consistent with a role for Tyr317 in the feedback inhibition of Jak2 kinase activity after receptor stimulation. Comparison to several previously identified regulatory phosphorylation sites on Jak2 revealed a dominant role for Tyr317 in the attenuation of Jak2 signaling. In contrast, mutation of Tyr637 decreased Jak2 signaling and activity and partially suppressed the activating JH2 V617F mutation, suggesting a role for Tyr637 phosphorylation in the release of JH2 domain-mediated suppression of Jak2 kinase activity during cytokine stimulation. The phosphorylation of Tyr317 and Tyr637 act in concert with other regulatory events to maintain appropriate control of Jak2 activity and cytokine signaling.

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.

Molecular characterization of a thyroid tumor-specific transforming sequence formed by the fusion of ret tyrosine kinase and the regulatory subunit RI alpha of cyclic AMP-dependent protein kinase A

1993 ◽  
Vol 13 (1) ◽  
pp. 358-366
Author(s):  
I Bongarzone ◽  
N Monzini ◽  
M G Borrello ◽  
C Carcano ◽  
G Ferraresi ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Cyclic Amp ◽  
Tyrosine Kinase ◽  
Kinase Domain ◽  
Regulatory Subunit ◽  
Tyrosine Kinase Domain ◽  
Papillary Thyroid ◽  
Thyroid Carcinomas ◽  
Kinase A

The ret oncogene frequently has been found activated in papillary thyroid carcinomas. A previous characterization of ret activation revealed recombination of its tyrosine kinase domain and sequences derived from an uncharacterized locus (D10S170). The mechanism leading to this recombination was identified as a paracentric inversion of the long arm of chromosome 10, inv(10)(q11.2q21), with the breakpoints occurring where ret and D10S170 were mapped. To further characterize the activation of ret in papillary thyroid carcinomas, we have now isolated and sequenced a second type of ret oncogenic rearrangement not involving the D10S170 locus. The nucleotide sequence indicated that the transforming activity was created by the fusion of the ret tyrosine kinase domain with part of the RI alpha regulatory subunit of protein kinase A (PKA). This is the first example of an oncogenic activity involving a PKA gene. PKA is the main intracellular cyclic AMP receptor, and its RI alpha subunit gene is located on chromosome 17q. RI alpha-ret transcripts encode two isoforms of the chimeric protein (p76 and p81), which display constitutive tyrosine phosphorylation as well as a tyrosine kinase enzymatic activity. Under nonreducing conditions, both isoforms are found in a dimeric configuration because of both homo- and heterodimer formation. Thus, the in vivo activation of ret in human papillary thyroid carcinomas is provided by the fusion of its tyrosine kinase domain with different genes and can be mediated by different mechanisms of gene rearrangement.

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