Structure of the protein tyrosine kinase domain of C-terminal Src kinase (CSK) in complex with staurosporine 1 1Edited by I. A. Wilson

1999 ◽  
Vol 285 (2) ◽  
pp. 713-725 ◽  
Author(s):  
Marieke B.A.C Lamers ◽  
Alfred A Antson ◽  
Roderick E Hubbard ◽  
Richard K Scott ◽  
David H Williams
Keyword(s):  
Tyrosine Kinase ◽  
Protein Tyrosine Kinase ◽  
Src Kinase ◽  
Kinase Domain ◽  
Tyrosine Kinase Domain ◽  
Protein Tyrosine

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 Crystal structure of the EphA4 protein tyrosine kinase domain in the apo- and dasatinib-bound state

FEBS Letters ◽  
2011 ◽  
Vol 585 (22) ◽  
pp. 3593-3599 ◽  
Author(s):  
Carine Farenc ◽  
Patrick H.N. Celie ◽  
Cornelis P. Tensen ◽  
Iwan J.P. de Esch ◽  
Gregg Siegal
Keyword(s):  
Crystal Structure ◽  
Tyrosine Kinase ◽  
Protein Tyrosine Kinase ◽  
Bound State ◽  
Kinase Domain ◽  
Tyrosine Kinase Domain ◽  
Protein Tyrosine

scholarly journals Crystal Structures of the Lyn Protein Tyrosine Kinase Domain in Its Apo- and Inhibitor-bound State

2008 ◽  
Vol 284 (1) ◽  
pp. 284-291 ◽  
Author(s):  
Neal K. Williams ◽  
Isabelle S. Lucet ◽  
S. Peter Klinken ◽  
Evan Ingley ◽  
Jamie Rossjohn
Keyword(s):  
Tyrosine Kinase ◽  
Crystal Structures ◽  
Protein Tyrosine Kinase ◽  
Bound State ◽  
Kinase Domain ◽  
Tyrosine Kinase Domain ◽  
Protein Tyrosine

scholarly journals 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.

Mutations in the tyrosine kinase domain of FLT3 define a new molecular mechanism of acquired drug resistance to PTK inhibitors in FLT3-ITD–transformed hematopoietic cells

Blood ◽  
2004 ◽  
Vol 103 (6) ◽  
pp. 2266-2275 ◽  
Author(s):  
Ksenia Bagrintseva ◽  
Ruth Schwab ◽  
Tobias M. Kohl ◽  
Susanne Schnittger ◽  
Sabine Eichenlaub ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Tyrosine Kinase ◽  
Cell Lines ◽  
Protein Tyrosine Kinase ◽  
Kinase Domain ◽  
Genetic Alterations ◽  
Tyrosine Kinase Domain ◽  
Protein Tyrosine ◽  
Clinical Resistance ◽  
Transformed Cell Lines

Abstract Activating mutations in the juxtamembrane domain (FLT3-length mutations, FLT3-LM) and in the protein tyrosine kinase domain (TKD) of FLT3 (FLT3-TKD) represent the most frequent genetic alterations in acute myeloid leukemia (AML) and define a molecular target for therapeutic interventions by protein tyrosine kinase (PTK) inhibitors. We could show that distinct activating FLT3-TKD mutations at position D835 mediate primary resistance to FLT3 PTK inhibitors in FLT3-transformed cell lines. In the presence of increasing concentrations of the FLT3 PTK inhibitor SU5614, we generated inhibitor resistant Ba/F3 FLT3-internal tandem duplication (ITD) cell lines (Ba/F3 FLT3-ITD-R1-R4) that were characterized by a 7- to 26-fold higher IC50 (concentration that inhibits 50%) to SU5614 compared with the parental ITD cells. The molecular characterization of ITD-R1-4 cells demonstrated that specific TKD mutations (D835N and Y842H) on the ITD background were acquired during selection with SU5614. Introduction of these dual ITD-TKD, but not single D835N or Y842H FLT3 mutants, in Ba/F3 cells restored the FLT3 inhibitor resistant phenotype. Our data show that preexisting or acquired mutations in the PTK domain of FLT3 can induce drug resistance to FLT3 PTK inhibitors in vitro. These findings provide a molecular basis for the evaluation of clinical resistance to FLT3 PTK inhibitors in patients with AML.

Diverse expression of dsrc29A, a gene related to src, during the life cycle of Drosophila melanogaster

Development ◽  
1990 ◽  
Vol 110 (4) ◽  
pp. 1169-1183
Author(s):  
A.L. Katzen ◽  
T. Kornberg ◽  
J.M. Bishop
Keyword(s):  
Life Cycle ◽  
Tyrosine Kinase ◽  
Protein Tyrosine Kinase ◽  
Kinase Domain ◽  
Tyrosine Kinase Domain ◽  
Phagocytic Cells ◽  
Kinase Gene ◽  
Protein Tyrosine ◽  
Tyrosine Kinase Gene

We used in situ hybridization to study the RNA expression of the dsrc29A gene during Drosophila development. This gene encodes two proteins differing at their amino termini. Both gene products contain a protein-tyrosine kinase domain and resemble the protein encoded by vertebrate src. We examined most stages of development in the Drosophila life cycle: embryos, third instar larvae, pupae and adults. Our results revealed that dsrc29A expression is specialized throughout development, being prominent at various times in neural tissue, phagocytic cells, dorsal vessel, ovaries, gut, developing salivary glands, imaginal discs and disc derivatives. These findings confirm and extend previous results for the distribution of dsrc29A protein, indicating that the regulation of this gene is primarily at the level of transcription. In some tissues expression is transient, whereas in others, it is continuous, and expression occurs in proliferative, differentiating and differentiated tissue. These patterns of expression demonstrate how a single protein-tyrosine kinase might play diverse roles at different times during development. Comparison of the expression of dsrc29A and other members of the protein-tyrosine kinase gene superfamily reveals that the genes are expressed in distinctive but sometimes overlapping patterns.

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.

Activation of c-Src in cells bearing v-Crk and its suppression by Csk

1992 ◽  
Vol 12 (10) ◽  
pp. 4706-4713
Author(s):  
H Sabe ◽  
M Okada ◽  
H Nakagawa ◽  
H Hanafusa
Keyword(s):  
Tyrosine Kinase ◽  
Tyrosine Phosphorylation ◽  
Protein Tyrosine Kinase ◽  
Kinase Activity ◽  
Src Kinase ◽  
Cellular Protein ◽  
Morphological Transformation ◽  
Protein Tyrosine ◽  
In Cells

The protein product of the CT10 virus, p47gag-crk (v-Crk), which contains Src homology region 2 (SH2) and 3 (SH3) domains but lacks a kinase domain, is believed to cause an increase in cellular protein tyrosine phosphorylation. A candidate tyrosine kinase, Csk (C-terminal Src kinase), has been implicated in c-Src Tyr-527 phosphorylation, which negatively regulates the protein tyrosine kinase of pp60c-src (c-Src). To investigate how c-Src kinase activity is regulated in vivo, we first looked at whether v-Crk can activate c-Src kinase. We found that cooverexpression of v-Crk and c-Src caused elevation of c-Src kinase activity, resulting in an increase of tyrosine phosphorylation of cellular proteins and morphological transformation of rat 3Y1 fibroblasts. v-Crk and c-Src complexes were not detected, although v-Crk bound to a variety of tyrosine-phosphorylated proteins in cells overexpressing v-Crk and c-Src. Overexpression of Csk in these transformed cells caused reversion to normal phenotypes and also reduced the level of c-Src kinase activity. However, Csk did not cause reversion of cells transformed by v-Src or c-Src527F, in which Tyr-527 was changed to Phe. These results strongly suggest that Csk acts on Tyr-527 of c-Src and suppresses c-Src kinase activity in vivo. Because Csk can suppress transformation by cooverexpression of v-Crk and c-Src, we suggest that v-Crk causes activation of c-Src in vivo by altering the phosphorylation state of Tyr-527.

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