Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Tyrosine phosphorylation of IQGAP1 in the MET pathway

ABSTRACT: Mass spectrometry was used to determine IQGAP1 is a substrate of MET and c-Src, and is phosphorylated exclusively on Tyr-1510 under conditions with enhanced MET or c-Src cellular activity.

INSTRUMENT(S): Q Exactive Plus

ORGANISM(S): Human

SUBMITTER: Dean McNulty

PROVIDER: MSV000086089 | MassIVE |

SECONDARY ACCESSION(S): PXD021327

REPOSITORIES: MassIVE

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Publications

Tyrosine phosphorylation of the scaffold protein IQGAP1 in the MET pathway alters function.

Hedman Andrew C AC McNulty Dean E DE Li Zhigang Z Gorisse Laëtitia L Annan Roland S RS Sacks David B DB

The Journal of biological chemistry 20201021 52

IQGAP1 is a key scaffold protein that regulates numerous cellular processes and signaling pathways. Analogous to many other cellular proteins, IQGAP1 undergoes post-translational modifications, including phosphorylation. Nevertheless, very little is known about the specific sites of phosphorylation or the effects on IQGAP1 function. Here, using several approaches, including MS, site-directed mutagenesis, siRNA-mediated gene silencing, and chemical inhibitors, we identified the specific tyrosine ...[more]

PMID: 33087447

Similar Datasets

Tyrosine phosphorylation of IQGAP1 in the MET pathway

Project description:Mass spectrometry was used to determine that cellular IQGAP1 and IQGAP2 proteins are phosphorylated at multiple tyrosine residues upon sodium orthovanadate treatment.

| MSV000086088 | MassIVE

In vitro tyrosine phosphorylation of ALIX

Project description:Human ALIX (Uniprot accession no. Q8WUM4) Bro1 and proline-rich domains were recombinantly expressed, purified, and phosphorylated in vitro by tyrosine kinase Src. Phosphorylation products were analyzed by mass spectrometry.

| MSV000088057 | MassIVE

Members of the Plant CRK-superfamily are Capable of trans-/auto-Phosphorylation of Tyrosine Residues

Project description:Protein phosphorylation on Tyr residues is a key post-translational modification in mammals. In plants, recent studies have identified Tyr-specific protein phosphatase and Tyr-phosphorylated proteins in Arabidopsis by phosphoproteomic screenings, implying that plants have a Tyr phosphorylation signal pathway. However, little is known about the protein kinases (PKs) involved in Tyr phosphorylation in plants. Here, we demonstrate that Arabidopsis calcium-dependent protein kinase (CDPK/CPK)-related PKs (CRKs) have high Tyr autophosphorylation activity and that they can phosphorylate Tyr residue(s) on substrate proteins in Arabidopsis. In order to identify PKs for Tyr phosphorylation, we examined the autophosphorylation activity of 759 PKs using an Arabidopsis protein array based on a wheat cell-free system. In total, we identified 38 PKs with Tyr autophosphorylation activity. The CRK family was a major protein family identified. A cell-free substrate screening revealed that these CRKs phosphorylate beta-tubulin (TBB) 2, TBB7 and certain transcription factors (TFs) such as ethylene response factor 13 (ERF13). All five CRKs tested showed Tyr auto/trans-phosphorylation activity and especially two CRKs, CRK2 and CRK3, showed a high ERF13 Tyr phosphorylation activity. A cell-based transient expression assay revealed that Tyr16/207 sites in ERF13 were phosphorylated by CRK3 and that Tyr phosphorylation of endogenous TBBs occurs in CRK2 overexpressing cells. Furthermore, crk2 and crk3 mutants showed a decrease in the Tyr phosphorylation level of TBBs. These results suggest that CRKs have Tyr kinase activity, and these might be one of the major PKs responsible for protein Tyr-phosphorylation in Arabidopsis plants.

2018-10-24 | PXD002158 | Pride

CTD tyrosine phosphorylation impairs termination factor recruitment to transcribing RNA polymerase II

Project description:ChIP-chip was performed to identify the genomic binding locations for the termination factors Nrd1, and Rtt103, and for RNA polymerase (Pol) II phosphorylated at the tyrosine 1 and threonine 4 position of its C-terminal domain (CTD). In different phases of the transcription cycle, Pol II recruits different factors via its CTD, which consists of heptapeptide repeats with the sequence Tyr1-Ser2-Pro3-Thr4-Ser5-Pro6-Ser7. Here we show that the CTD of transcribing yeast Pol II is phosphorylated at Tyr1, and that this impairs recruitment of termination factors. Tyr1 phosphorylation levels rise downstream of the transcription start site (TSS), and decrease before the polyadenylation (pA) site. Tyr1-phosphorylated gene bodies are depleted of CTD-binding termination factors Nrd1, Pcf11, and Rtt103. Tyr1 phosphorylation blocks CTD binding by these termination factors, but stimulates binding of elongation factor Spt6. These results show that CTD modifications can not only stimulate but also block factor recruitment, and lead to an extended CTD code for transcription cycle coordination.

2012-06-29 | E-MTAB-1060 | biostudies-arrayexpress

Response of E. coli to m-Tyrosine

Project description:To ensure faithful translation of the genetic code, some aminoacyl-tRNA synthetases have a quality control (QC) mechanism that allows them to remove similarly shaped, non-protein amino acids (NPAs) from a mischarged tRNA. In E. coli, the QC function of phenyalanyl-tRNA synthetase (PheRS) is required for resistantce to the toxic NPA, meta-Tyrosine (m-Tyr). Here, we sought to understand the mechanism of m-Tyr toxicity. Using RNA-seq, we observed >500 genes were differential expressed after the addition of m-Tyr. The most strongly up-regulated genes are involved in unfolded-protein stress response, and cells exposed to m-Tyr contained large, electron-dense protein aggregates, indicating that m-Tyr destabilized a large fraction of the proteome. Additionally, we observed that amino acid biosynthesis and transport regulons, controlled by ArgR, TrpR, and TyrR, and the stringent-response regulon, controlled by DksA/ppGpp, were differentially expressed. m-Tyr resistant mutants were isolated and found to have altered a promoter to increase expression of the enzymes for Phe production or to have altered transporters, which likely result in less uptake or increased efflux of m-Tyr. These findings indicate that QC by PheRS is the critical point for resisting the toxic effects of m-Tyr, when m-Tyr has passed the QC checkpoint and enters the proteome, it is sequestered in protein aggregates that are eventually lost through cell division.

2020-11-30 | GSE140211 | GEO

An allosteric switch between the activation loop and a c-terminal palindromic phospho-motif drives c-Src disfunction in cancer

Project description:The allosteric mechanisms that control the different functional and conformational states of oncogenic kinases, and how these molecular switches can be targeted and therapeutically exploited remains largely unexplored. Here we show that c-terminal Tyr 530 is a de facto c- Src auto-phosphorylation site with slow time-resolution kinetics and strong intermolecular component. On the contrary, activation-loop Tyr 419 undergoes fast kinetics and a cis-to-trans phosphorylation-switch that controls c-terminal Tyr 530 phosphorylation, enzyme specificity and strikingly, c-Src non-catalytic function as a substrate. In line with this, we visualize by X-ray crystallography a snapshot of c-terminal Tyr 530 intermolecular phosphorylation between the enzyme and susbtrate acting kinases, and identify a functionally relevant c-terminal palindromic phospho-motif flanking Tyr 530 making important contacts at the interface. Perturbation of this phospho-motif accounts for c-Src disfunction in cancer, as indicated by viral and a colorectal cancer (CRC) associated c-terminal deleted variants. We show that c-terminal residues 531 to 536 are required for c-Src Tyr 530 auto-phosphorylation and overall phospho-tyrosine activity. However, c-terminal truncated forms display a minor delay in the capacity to phosphorylate intact c-Src substrates surrogates. On the contrary, when these c-terminal variants were used as intact substrate surrogates themselves, they were equally and efficiently phosphorylated, but strikingly they resulted in the allosteric inhibition of the active kinase. Our work reveals a bi-directional crosstalk between activation and c-terminal segments driven by auto-phosphorylation that controls the allosteric interplay between enzyme and susbtrate acting kinases. These findings have important implications for the drug-design and development of next generation c-Src inhibitors targeting non-catalytic and/or allosteric vulnerabilities.

2023-09-04 | PXD037287 | Pride

Targeted metabolic profiling of tyrosine in urine for colorectal cancer diagnosis

Project description:Interventions: Gold Standard:;Index test: Primary outcome(s): the urinary Tyr test Study Design: Diagnostic test for accuracy

| 2662420 | ecrin-mdr-crc

Postprandial FGF19 signaling-induced phosphorylation of FXR by Src modulates its activity in bile acid homeostasis

Project description:Farnesoid-X-Receptor (FXR) plays a central role in maintaining bile acid (BA) homeostasis by transcriptional control of numerous enterohepatic genes, including intestinal FGF19, a hormone that strongly represses hepatic BA synthesis. How activation of the FGF19 receptor at the membrane is transmitted to the nucleus for transcriptional regulation of BA levels and whether FGF19 signaling posttranslationally modulates function of FXR remain largely unknown. Here we show that FXR is phosphorylated at Y67 by non-receptor tyrosine kinase, Src, in response to postprandial FGF19, which is critical for its nuclear localization and transcriptional regulation of BA levels. Liver-specific expression of phospho-defective Y67F-FXR or Src-downregulation in mice result in impaired homeostatic responses to acute BA feeding, and exacerbate cholestatic pathologies upon drug-induced hepatobiliary insults. Also, the hepatic FGF19-Src-FXR pathway is defective in primary biliary cirrhosis patients. This study identifies Src-mediated FXR phosphorylation as a potential therapeutic target and biomarker for BA-related enterohepatic diseases.

2018-04-27 | GSE113707 | GEO

Transcription profiling of doxorubicin sensitive and resistant human myeloma cell lines after treatment with doxorubicin to explore the role of the STAT1 signaling pathway in drug and radiation resistance

Project description:The myeloma cell line RPMI 8226/S and its doxorubicin resistant subline 8226/Dox40 were used as models to explore the potential importance of the STAT1 signaling pathway in drug and radiation resistance. The 40-fold doxorubicin resistant subline 8226/Dox40 was found to be crossresistant to single doses of 4 and 8 Gy of radiation. A genome-wide mRNA expression study comparing the 8226/Dox40 cell line to its parental line was performed to identify the underlying molecular mechanisms. Seventeen of the top 50 overexpressed genes have previously been implicated in the STAT1 signaling pathway. STAT1 was over expressed both at the mRNA and protein level. Moreover, analyses of nuclear extracts showed higher abundance of phosphorylated STAT1 (Tyr 701) in the resistant subline. Preexposure of the crossresistant cells to the STAT1 inhibiting drug fludarabine reduced expression of overexpressed genes and enhanced the effects of both doxorubicin and radiation. These results show that resistance to doxorubicin and radiation is associated with increased STAT1 signaling and can be modulated by fludarabine. The data support further development of therapies combining fludarabine and radiation.

2007-01-10 | E-BASE-2 | biostudies-arrayexpress

Evaluation of phospho-tyrosine antibodies for label-free phosphoproteomics

Project description:In the past decade multiple tyrosine kinase inhibitors (TKIs) have been implemented in standard treatment regimens for patients with cancer. Unfortunately the majority of patients develops resistance to these drugs. Reliable tools for analysis of pharmacodynamic effects and drug resistance mechanisms are therefore warranted. Phosphoproteomics has meanwhile emerged as tool for the analysis of tyrosine protein phosphorylation. These studies rely on antibodies for enrichment of tyrosine-phosphorylated peptides. Here we compared two commercially available phosphotyrosine antibodies and show that P-Tyr-1000 yields 64% more phosphopeptides than the 4G10 antibody. To investigate performance of P-Tyr-1000 in a label-free comparative phosphoproteomics analysis, a commonly used cell culture model was employed. U87 glioma cells with or without EGFRvIII mutation, lacking the extracellular ligand binding domains (exon 2 - 7) and displaying constitutive signaling activity, were analyzed with the workflow described above. U87 cells and the isogenic version with EGFRvIII were both treated with or without the TKI Erlotinib. In total 1330 phosphopeptides were detected derived from 683 phosphorylated proteins.

2015-12-09 | PXD001565 | Pride

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data