Domains recognize peptide ligands phosphotyrosine binding domain. Medical search. Frequent questions

In the case of the mitochondrial P450 systems, the specific residues involved in the binding of the electron transfer protein adrenodoxin to its reductase were identified as two basic Arg residues on the surface of the reductase and two acidic Asp residues on the adrenodoxin. (wikipedia.org)
Different families of SH2 domains may have different binding specificity, which is usually determined by a few residues C-terminal with respect to the pY (positions +1 to +4). (eu.org)
The residue at pY+2 does not make direct side chain interactions with the SH2 domain, but aromatic residues are not allowed. (eu.org)
Positively charged residues are disfavoured at pY-1 and pY-2 due to the positively charged SH2 domain surface, but are tolerated when pY+1 and pY+3 are strong residues. (eu.org)
The name WW or WWP derives from the presence of two signature tryptophan residues that are spaced 20-23 amino acids apart and are present in most WW domains known to date, as well as that of a conserved Pro. (embl.de)
An important consequence of reversible phosphorylation of tyrosine residues on proteins is the creation of binding sites for phosphotyrosine recognizing domains such as Src homology 2 (SH2) and phosphotyrosine binding (PTB) domains [ 1 , 2 ]. (biomedcentral.com)
This is consistent with reports that the slow phosphorylation of tyrosine residues of the Lat adaptor associates with recruitment and activation of the phospholipase Plcγ1, thereby constituting an important kinetic bottleneck for ligand discrimination 11 . (nature.com)
While the phosphorylation of tyrosine residues in the immunoreceptor tyrosine-based activation motifs (ITAMs) of Cd3 and the inducible interaction between Cd3 and Zap70 remained largely unaffected, the abundance of activated Zap70 dropped with decreasing peptide affinity. (nature.com)
There are no totally invariant residues within the PH domain. (embl.de)
Isoform gamma contains two PH domains, the second one is split into two parts separated by about 400 residues. (embl.de)

Src Homology 2 (SH2) domains are small modular domains found within a great number of proteins involved in different signalling pathways. (eu.org)
There is a great interest in studying phosphotyrosine dependent protein-protein interactions in tyrosine kinase pathways that play a critical role in many aspects of cellular function. (biomedcentral.com)
In particular, it is unclear whether ligand affinity uniformly affects the different signaling pathways involved in T cell activation. (nature.com)
Our analysis indicated that ligand affinity differentially affected signaling pathways associated with specific kinases and biological processes. (nature.com)
EphB4 over-production promotes ligand-independent signaling pathways that increase cancer cell viability and stimulate migration and invasion. (oncotarget.com)
Through these interactions, PH domains play a role in recruiting proteins to different membranes, thus targeting them to appropriate cellular compartments or enabling them to interact with other components of the signal transduction pathways. (embl.de)

Despite significant promiscuity between other Eph family members and the ephrin ligands, the single physiologically-relevant ligand of the EphB4 receptor is ephrin-B2 [ 2 ]. (oncotarget.com)
Over-expression of endogenous fly Eph and RNAi-mediated knock-down of Eph and its ligand ephrin affected sleep architecture and neurophysiology. (sdbonline.org)

GTP binding to SRP and SRP receptor is a prerequisite for SRP / SRP receptor complex formation. (mechanobio.info)
Following the complex positioning (3), SRP / SRP receptor complex dissociates from the peptide due to GTP hydrolysis. (mechanobio.info)
According to the kinetic proofreading model, antigen discrimination properties could be explained by the gradual amplification of small differences in binding affinities as the signal is transduced downstream of the T cell receptor. (nature.com)
Although low-affinity ligands induced phosphorylation of the Cd3 chains of the T cell receptor and the interaction of Cd3 with the Zap70 kinase as strongly as high-affinity ligands, they failed to activate Zap70 to the same extent. (nature.com)
As a result, formation of the signalosome of the Lat adaptor was severely impaired with low- compared with high-affinity ligands, whereas formation of the signalosome of the Cd6 receptor was affected only partially. (nature.com)
T cells have the ability to sense and discriminate a wide range of antigenic peptides bound to major histocompatibility complex (pMHC) molecules according to their affinity for the T cell receptor (TCR). (nature.com)
The mechanism of host cell invasion by SARS-CoV-2 involves the interaction of angiotensin-converting enzyme (ACE2) with receptor-binding domain (RBD) of spike protein (S). The main protease (Mpro/3CLpro) is an attractive drug target due to its vital function in regulation of polyprotein translated from viral RNA. (bvsalud.org)
EphB4 is a membrane-bound receptor tyrosine kinase (RTK) commonly over-produced by many epithelial cancers but with low to no expression in most normal adult tissues. (oncotarget.com)
Both the receptor and the ligand are membrane-bound but usually expressed on neighbouring cells. (oncotarget.com)
The α-adrenergic receptor is described by seven α-helical transmembrane (TM) domains which form a 'crevice' for ligand binding. (pharmacology2000.com)
By analyzing specific amino acid mutations of the α 2A - receptor with respect to changes in PB binding, certain sites were identified that may serve as the molecular target for phenoxybenzamine-mediated receptor blockade. (pharmacology2000.com)
For example, if a particular cysteine residue located in the TM3 domain was changed to valine (by mutation), the receptor becomes resistant to phenoxybenzamine inactivation. (pharmacology2000.com)
This can either occur by cell surface receptor interactions, as in the case with peptide growth factors, or by interactions with intracellular molecules, as in the case with steroid hormones. (beauty104.com.tw)
2003). FGF molecules bind to a family of receptor molecules consisting of 4 members (FGFR1, FGFR2, FGFR3, and FGFR4). (beauty104.com.tw)
Results DIM, but not I3C, increased adipocyte differentiation through upregulation of peroxisome proliferator‐activated receptor γ and CCAAT/enhancer‐binding protein α. (researchgate.net)

SH2 binding kinetics determined by PLA-SH2 showed good agreement with established far-Western analyses for A431 and Cos1 cells stimulated with EGF at various times and doses. (biomedcentral.com)
Small differences in binding kinetics between TCR ligands lead to marked differences in T cell effector function and differentiation. (nature.com)
Here, we study the dissociation kinetics of tubulin:stathmin assemblies in presence of different tubulin-binding proteins and identify a critical role of the C-terminus of the stathmin partner. (bvsalud.org)

We previously established SH2 profiling, a phosphoproteomic approach based on membrane binding assays that utilizes purified Src Homology 2 (SH2) domains as a molecular tool to profile the global tyrosine phosphorylation state of cells. (biomedcentral.com)
SH2 profiling is a unique proteomic method in which interactions between an array of SH2 domains and protein samples are quantitatively analyzed, thereby defining the functional output of tyrosine phosphorylation. (biomedcentral.com)
Here, we used time-resolved high-throughput proteomic analyses to identify and quantify the phosphorylation events and protein-protein interactions encoding T cell ligand discrimination in antigen-experienced T cells. (nature.com)
We defined quantitative signatures of ligand affinity based on protein phosphorylation and protein-protein interaction (PPI) stoichiometry for critical molecular events associated with TCR signaling. (nature.com)
Addition of antibody to cancer cells resulted in phosphorylation and subsequent degradation of the EphB4 protein, suggesting a mechanism that is ligand mimetic and tumour suppressive. (oncotarget.com)
In this study we used phosphorylation of the transcription factor cAMP response element-binding protein as a functional readout to identify cells responding to EGF and FGF-2. (beauty104.com.tw)
phosphorylation of STAT1: this peptide inhibited proliferation of prostate cancer cell lines, in which STAT3 is constitutively activated. (micrornaarray.com)

The Tir protein of EPEC binds NCK1/NCK2 SH2 domains through a high affinity pYDEV motif ( Frese,2006 ). (eu.org)
Val and Pro confer high-affinity binding at pY+3 - Ala and Ile are tolerated but confer weaker binding. (eu.org)
T cells recognize a few high-affinity antigens among a vast array of lower affinity antigens. (nature.com)

The Src Homology 2 (SH2) domain is a major protein interaction module that is central to tyrosine kinase signaling. (eu.org)
Pleckstrin homology domain. (embl.de)
Pleckstrin homology (PH) domains are small modular domains that occur in a large variety of proteins. (embl.de)
Although these factors possess remarkably similar sequence homology, they do not bind FGFRs and are involved in intracellular processes unrelated to the FGFs (Olsen et al. (beauty104.com.tw)

The SH2-PLA assay utilizes oligonucleotide-conjugated anti-GST and anti-EGFR antibodies recognizing a GST-SH2 probe and cellular EGFR, respectively. (biomedcentral.com)
If the GST-SH2 and EGFR are in close proximity as a result of SH2-phosphotyrosine interactions, the two oligonucleotides are brought within a suitable distance for ligation to occur, allowing for efficient complex amplification via real-time PCR. (biomedcentral.com)
The assay detected signal across at least 3 orders of magnitude of lysate input with a linear range spanning 1-2 orders and a low femtomole limit of detection for EGFR phosphotyrosine. (biomedcentral.com)
We showed for the first time that interactions between SH2 domain probes and EGFR in cell lysate can be determined in a microliter-scale assay using SH2-PLA. (biomedcentral.com)
Interestingly, aux depletion causes a dramatic increase in EGFR signaling, with a strong accumulation of EGFR at the plasma membrane and an increased expression of EGFR ligands in response to tissue stress. (sdbonline.org)

Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. (embl.de)

The chromo-domain binds histone H3 tails methylated on lysine 9. (cipsm.de)

These interactions between proteins are dependent on highly specific binding between proteins to ensure efficient electron transfer. (wikipedia.org)
In addition to the conventional complexes, as enzyme-inhibitor and antibody-antigen, interactions can also be established between domain-domain and domain-peptide. (wikipedia.org)
They are able to bind specific motifs containing a phosphorylated tyrosine residue, propagating the signal downstream by promoting protein-protein interactions and/or modifying enzymatic activities. (eu.org)
In NCK SH2 domains, the EF loop is positioned away from the BG loop, exposing the pY+3 binding pocket where the side chain of Val forms tight interactions. (eu.org)
SH2 domains are phosphotyrosine recognition domains, often mediating transient interactions with target proteins. (eu.org)
WW domain-mediated interactions reveal a spliceosome-associated protein that binds a third class of proline-rich motif: the proline glycine and methionine-rich motif. (embl.de)
In yeast, this bridging involves interactions between the WW domains in the splicing factor PRP40 and a proline-rich domain in the branchpoint binding protein, BBP. (embl.de)
This feature along with short assay runtime makes this method a useful platform for the development of high throughput assays to determine modular domain-ligand interactions which could have wide-ranging applications in both basic and translational cancer research. (biomedcentral.com)
Expression of the Escherichia coli tryptophanase operon depends on ribosome stalling during translation of the upstream TnaC leader peptide, a process for which interactions between the TnaC nascent chain and the ribosomal exit tunnel are critical. (cipsm.de)
Furthermore, structural analysis of particular TM domains suggested locations for phenoxybenzamine covalent interactions. (pharmacology2000.com)
The FGFs are heparin -binding proteins and interactions with cell-surface associated heparan sulfate proteoglycans has been shown to be essential for FGF signal transduction. (beauty104.com.tw)

Here we report the selection of camelid-derived single-domain antibodies (nanobodies) that modulate the conformation and spectral properties of the green fluorescent protein (GFP). (cipsm.de)
Regardless of the need for Th2 cells and their connected cytokines in the pathogenesis of sensitive respiratory disease, research of antigens regarded as causes of T-cell reactions have up to now been mostly limited by those recognized to bind IgE antibodies (7, 8) and induce IgE-mediated instant hypersensitivity reactions (9). (enmd-2076.com)

Mouse protein citron, a putative rho/rac effector that binds to the GTP-bound forms of rho and rac. (embl.de)

For example, many membrane bound proteins carry signal peptides that are recognized by signal receptors that guide them to the target site. (mechanobio.info)
The communication in subunit: enabling lymphoid GT-domains preventing membrane as a subunits addition: A ATM identified to the Faculty of Graduate Studies and Research in isolated pore of the heterotrimers for the use of Master of Nursing. (evakoch.com)

A large variety of proteins containing the WW domain are known. (embl.de)

Relating to this idea, particular B cells internalize and procedure the antigen, resulting in the demonstration of antigen fragments destined by surface area MHC course II molecules that may be recognized EI1 by particular T cells guaranteeing how the T cells deliver help B cells particular for the same antigen (connected help). (enmd-2076.com)
Adaptive immune mechanisms recognize and neutralize foreign molecules or microorganisms in a specific manner. (lu.se)

Several different binding motifs are known, for example: pYEEI (Src-family SH2 domains), pY [IV]. (eu.org)
The C-terminal half of the SH2 domain exhibits greater structural variability and provides a platform for accommodating different kinds of SH2-binding motifs. (eu.org)
Zinc finger (Znf) domains are relatively small protein motifs which contain multiple finger-like protrusions that make tandem contacts with their target molecule. (embl-heidelberg.de)
They display considerable versatility in binding modes, even between members of the same class (e.g. some bind DNA, others protein), suggesting that Znf motifs are stable scaffolds that have evolved specialised functions. (embl-heidelberg.de)
Zinc-binding motifs are stable structures, and they rarely undergo conformational changes upon binding their target. (embl-heidelberg.de)

The human NCK1 (Nckα) and NCK2 (Nckβ/GRB4) SH2 domains show a degree of partner specificity but share the same mode of ligand binding ( Frese,2006 ) and belong to the class IA family which contains an aromatic residue (Phe) at the specificity-determining βD5 position ( Kaneko,2010 ). (eu.org)
Three loops surround the peptide binding pocket and are important for specificity: Because these loops can be flexible, considerable variation in peptide binding can apply for any given SH2 domain. (eu.org)

The protease not only releases small peptides, such as the amyloid-β peptide, which drives Alzheimer's disease pathogenesis, but also intracellular domains, which can have critical functions in nuclear signaling. (cipsm.de)

The signaling complex at the cell surface is believed to be a ternary complex formed between two identical FGF ligands, two identical FGFR subunits and either one or two heparan sulfate chains. (beauty104.com.tw)

The 30 untranslated region of DRAM1 and BECN1 holding putative miR 199a 5p binding website were amplified by PCR from human Plastid genomic DNA of healthy blood donor. (ilreceptor.com)

The interaction between SH2 domains and their substrates is however dependent also on cooperative contacts of other surface regions. (eu.org)
Here, we used mass spectrometry (MS)-based methods to determine and quantify, in a time-dependent manner, early molecular events triggered following TCR stimulation with peptides of varying affinities. (nature.com)
Several studies have shown that normal ligand-dependent signaling is tumour suppressive and therefore novel therapeutics which block the tumour promoting ligand-independent signaling and/or stimulate tumour suppressive ligand-dependent signaling will find application in the treatment of cancer. (oncotarget.com)

We have developed PLA-SH2, an alternative in-solution modular domain binding assay that takes advantage of Proximity Ligation Assay and real-time PCR. (biomedcentral.com)

Not long after FGF1 and FGF2 were isolated, another group isolated a pair of heparin -binding growth factors which they named HBGF-1 and HBGF-2, whilst a third group isolated a pair of growth factors that caused proliferation of cells in a bioassay containing blood vessel endothelium cells which they called ECGF-1 and ECGF-2. (beauty104.com.tw)

Peptide exclusion was used to identify the epitope targeted by this antibody within the cysteine-rich region of the EphB4 protein, a sequence defined as a potential ligand interacting interface. (oncotarget.com)
Their binding properties depend on the amino acid sequence of the finger domains and of the linker between fingers, as well as on the higher-order structures and the number of fingers. (embl-heidelberg.de)

A monoclonal antibody which specifically targets this identified extracellular epitope of EphB4 significantly reduced breast cancer xenograft growth in vivo confirming that EphB4 is a useful target for ligand-mimicking antibody-based anti-cancer therapies. (oncotarget.com)

After it receives an electron, it dissociates and then binds to the next enzyme that acts as its oxidase (i.e. an acceptor of the electron). (wikipedia.org)

The obvious benefit of this method is that the low sample requirement allows detection of SH2 binding in samples which are difficult to analyze using traditional protein interaction assays. (biomedcentral.com)
The RING domain is a protein interaction domain that has been implicated in a range of diverse biological processes. (embl-heidelberg.de)

In the canonical mode of SH2 binding, regions on either side of the central β sheet are involved in ligand binding. (eu.org)
The divergence between signals induced by ligands with different affinities occurred early in the canonical TCR signaling cascade. (nature.com)

Point mutations cluster into the positively charged end of the molecule around the predicted binding site for phosphatidylinositol lipids. (embl.de)

Within this review, we summarize the functions that all of the Aurora kinases has in cancer biology and mitosis, and discuss the binding modes of Aurora A kinase inhibitors, the spot elements in the binding sites and the fortunate inhibitor components. (survivinpathway.com)

This really is the first study to determine the impact of 5 HT on the deafferented circuits in the mind which are recognized to reorganize after SCI and, at least in the neonatally spinalized type, contribute to functional recovery in-the form of increased weight backed actions. (ilreceptor.com)

The 3D structure of the zinc ligation system is unique to the RING domain and is referred to as the 'cross-brace' motif. (embl-heidelberg.de)

Click on the protein counts, or double click on taxonomic names to display all proteins containing WW domain in the selected taxonomic class. (embl.de)

In con trast, therapeutics based mostly on these newly recognized human host targets will avoid HIV virus from employing the hosts cellular mechanism for its daily life cycle and are insensitive to drug resistance. (hivprotease-signal.com)
The physiological significance of the newly recognized splice variants and their respective isoforms is at this time unknown. (srcinhibitors.com)

Myosin filaments act as molecular motors and by binding to actin enables filament sliding. (wikipedia.org)

Reactions against the dominating undescribed epitopes had been from the memory space T-cell subset and may even be recognized directly former mate vivo after Th2 cell enrichment. (enmd-2076.com)

Pleckstrin, the protein where this domain was first detected, is the major substrate of protein kinase C in platelets. (embl.de)
Pleckstrin is one of the rare proteins to contains two PH domains. (embl.de)

Siglec-E, a mouse orthologue of human Siglec-9, is a sialic acid binding lectin predominantly expressed on the surface of myeloid cells to transduce inhibitory signal via recruitment of SH2-domain containing protein tyrosine phosphatase SHP-1/2 upon binding to its sialoglycan ligands. (biomedcentral.com)

Which early molecular events are affected by ligand affinity, and how, has not been fully resolved. (nature.com)
Overall, this study provides a comprehensive map of molecular events associated with T cell ligand discrimination. (nature.com)

Mutations identified in many SH2 domain-containing proteins as well as the SH2 domain itself are associated with human diseases ranging from cancers, diabetes, to immunodeficiencies. (eu.org)

Several S. cerevisiae proteins involved in cell cycle regulation and bud formation like BEM2, BEM3, BUD4 and the BEM1-binding proteins BOI2 (BEB1) and BOI1 (BOB1). (embl.de)

that is, of the 182 amino acids defining the TM domains of the human α 2A -adrenergic receptors, about 40% are identical with the human β 2 -adrenergic receptors. (pharmacology2000.com)

Using a proline-rich domain derived from formin (a product of the murine limb deformity locus), we have identified a family of murine formin binding proteins (FBP's), each of which contains one or more of a special class of tyrosine-rich WW domains. (embl.de)
The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. (embl.de)
Siglecs are a family of sialic acid-binding immunoglobulin-like receptors predominantly expressed on cells of immune system to regulate their functions through recognizing their glycan ligands [ 5 ]. (biomedcentral.com)

These conserved regions appear to contain those structural elements needed for recognizing and binding various endogenous hormone/neurotransmitters (e.g. norepinephrine and epinephrine) as well as other ligands. (pharmacology2000.com)
The RPA gene is the structural excretion loss-of-function, However Binding it from the corresponding growth( De Laat et al. (evakoch.com)

This implies that the pMHC ligand dwell time on the TCR determines the probability of completing a series of signaling events leading to T cell activation 5 . (nature.com)

Regulators of small G-proteins like guanine nucleotide releasing factor GNRP (Ras-GRF) (which contains 2 PH domains), guanine nucleotide exchange proteins like vav, dbl, SoS and Saccharomyces cerevisiae CDC24, GTPase activating proteins like rasGAP and BEM2/IPL2, and the human break point cluster protein bcr. (embl.de)

However, in order to use this method to investigate SH2 binding sites on a specific target in cell lysate, additional procedures such as pull-down or immunoprecipitation which consume large amounts of sample are required. (biomedcentral.com)

The many processes involving SH2 domains range from mitogenic signaling to T cell activation. (eu.org)
Hence, how ligand affinity converts into signaling potency (that is, magnitude of T cell responses) remains unresolved. (nature.com)
Inside our earlier research of T-cell reactions against Timothy lawn (TG) things that trigger allergies (12), no relationship was recognized between IgE amounts and T-cell reactions in TG pollen-allergic people. (enmd-2076.com)
Infection of cells with oncolytic adenovirus CN305 SOCS3 and AdCN305 cell penetrating peptides SOCS3 resulted in buy Volasertib dramatic cytotoxicity of liver tumor cells. (micrornaarray.com)

It is frequently associated with other domains typical for proteins in signal transduction processes. (embl.de)

Note that in the older literature, some RING-fingers are denoted as LIM-domains. (embl-heidelberg.de)

The other two positions important for binding are pY+3 and pY+1. (eu.org)

Anatomy16

Organisms15

Chemicals and Drugs112

Analytical, Diagnostic and Therapeutic Techniques and Equipment41

Phenomena and Processes72

Disciplines and Occupations1

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Information Science4

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Residues10

Pathways6

Ephrin2

Receptor15

Kinetics3

Phosphorylation7

High-affinity3

Homology4

EGFR5

Tyrosine kinase1

Histone1

Interactions11

Antibodies2

Effector1

Membrane2

Large variety of proteins1

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Motifs5

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Protease1

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Putative1

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Antibody1

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Interaction2

Canonical2

Molecule1

Kinases1

Functional1

Ligation1

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Newly recognized2

Actin1

Vivo1

Pleckstrin2

Recruitment1

Molecular2

Mutations1

Proteins involved1

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