Ligands phosphotyrosine binding domain. Medical search. Frequent questions

In this study, we examined whether recurrent hypoglycemia alters the capacity of the ephrinA5 ligand to activate VMH EphA5 receptors, and if so, whether these changes could contribute to pathogenesis of defective glucose counterregulation in response to a standard hypoglycemic stimulus. (diabetesjournals.org)
Within the central nervous system, Eph receptors and their ligands, the ephrins, play a key role in cell-to-cell communication as well as in synaptic structure and function. (diabetesjournals.org)
Once a ligand has activated a receptor via dimerization, the Jaks transphosphorylate one another as well as the C-terminal tails of the receptors. (shu.edu)
Not shown here is the activation under certain conditions of Jaks that are bound to some G-protein-coupled receptors (GPCRs) and the phosphorylation of STATs directly by certain ligand-activated growth factor receptors (RTKs) as well as non-receptor tyrosine kinases. (shu.edu)
Using proteinCprotein connection assays, we shown that both SH2 and GEF domains of GIV are necessary for the forming of a ligand-activated ternary complicated between GIV, Gi, and development factor receptors as well as for activation of Gi after development factor stimulation. (bio-cavagnou.info)
For example, many membrane bound proteins carry signal peptides that are recognized by signal receptors that guide them to the target site. (mechanobio.info)
It binds to phosphotyrosine in the cytoplasmic tail of cell surface receptors via its central SH2 domain, and to its immediate downstream target. (elsevierpure.com)
c-Met and receptor originated from nantes (RON) are structurally related transmembrane phosphotyrosine kinase receptors. (oncotarget.com)
c-Met and RON form both activated homodimers and heterodimers with themselves and other families of phosphotyrosine kinase receptors. (oncotarget.com)
Aberrant expression and activities of c-Met and RON in cancer are attributed to various mechanisms including increased expression of their ligands or receptors and by activating mutations [ 4 , 15 ]. (oncotarget.com)
SH2 domains are around 100 amino acidity subunits that mediate the transduction of indicators via development of multiprotein complexes initiated by reputation and binding to choose phosphotyrosine residues on receptors and various other proteins [13]. (biospraysehatalami.com)
To develop a functional nervous system, axons must initially navigate through a complex environment, directed by guidance ligands and receptors. (silverchair.com)
The protein localizes to the plasma membrane andpericentrosomal vesicles, and binds to cell surface receptors, including CD4 and CD8, and othersignaling molecules. (sciencepop.org)
Although these receptors are structurally similar, they determine specificity for four ligands-GDNF, Neurturin (NRTN), Artemin (ARTN) and Persephin (PSPN). (medsci.org)
Receptors of this type are ubiquitous and transduce binding of a wide variety of extracellular ligands (peptide hormones, neurotransmitters and other bioactive compounds) into a physiological signal. (berkeley.edu)
Activation of adiponectin receptors (AdipoRs) by its natural ligand, adiponectin has been known to be involved in modulating critical metabolic processes such as glucose metabolism and fatty acid oxidation as demonstrated by a number of in vitro and in vivo studies over last two decades. (phoenixpeptide.com)

Src Homology 2 (SH2) domains are small modular domains found within a great number of proteins involved in different signalling pathways. (eu.org)
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)
SH2 domains are phosphotyrosine recognition domains, often mediating transient interactions with target proteins. (eu.org)
Domain commonly found in eukaryotic signalling proteins. (embl.de)
The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. (embl.de)
Pleckstrin homology (PH) domains are small modular domains that occur in a large variety of proteins. (embl.de)
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)
Pleckstrin is one of the rare proteins to contains two PH domains. (embl.de)
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)
Cytoskeletal proteins such as dynamin (see IPR001401 ), Caenorhabditis elegans kinesin-like protein unc-104 (see IPR001752 ), spectrin beta-chain, syntrophin (2 PH domains) and S. cerevisiae nuclear migration protein NUM1. (embl.de)
Oxysterol binding proteins OSBP, S. cerevisiae OSH1 and YHR073w. (embl.de)
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)
There are 196127 PH domains in 171590 proteins in SMART's nrdb database. (embl.de)
Taxonomic distribution of proteins containing PH domain. (embl.de)
The complete taxonomic breakdown of all proteins with PH domain is also avaliable . (embl.de)
Click on the protein counts, or double click on taxonomic names to display all proteins containing PH domain in the selected taxonomic class. (embl.de)
The resulting phosphotyrosines attract STAT proteins, such as the STAT1 and STAT2 shown here (dark blue, dark green), which bind via their SH2 domains and become phosphorylated on specific phosphotyrosines, indicated here as Y's (inset), by the Jaks. (shu.edu)
The growth factor receptor-binding protein Grb2, composed of one SH2 and two SH3 domains, acts as an adaptor protein in transduction of signals from tyrosine-phosphorylaled proteins (EGF-receptor, or SHC), to the Ras dependent pathways. (elsevierpure.com)
Here, we describe an approach called ''consolidated" ligands to probe structural and functional activities of multidomain proteins. (elsevierpure.com)
The ECM proteins bind to the extracellular domains of integrin heterodimers, whereas the actin stress fibers link to integrin cytoplasmic tails via large molecular complexes. (rupress.org)
Tyrosine phosphorylated regions in proteins function as specific binding sites for the SH2 domains containing cellular signalling proteins. (lu.se)
Receptor dimerization and autophosphorylation attracts proteins containing Src homology 2 (SH2) or phosphotyrosine binding (PTB) domains including adaptor proteins like FRS2 and GRB2. (springer.com)
Phosphorylation creates sites for protein-protein connections between your phosphorylated proteins and signaling substances formulated with SH2 and phosphotyrosine binding domains that recognize phosphotyrosine [13]. (biospraysehatalami.com)
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)
One limitation of current SH2 profiling methods is that these assays themselves do not provide the identity of the binding proteins. (biomedcentral.com)
16) also bind certain proteins and, hence, have also been used as affinity adsorbents. (dpforex.com)

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)
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)
Because positively charged residues in NT-3 are important for binding to trkB, two negatively charged aspartate residues within the 11 amino acid motif of FL trkB were mutated to examine the role of electrostatic interactions on ligand binding. (jneurosci.org)
Here, using baculoviral co-expression of the DDR2 cytosolic domain and Src, we show that Src targets three tyrosine residues (Tyr-736, Tyr-740, and Tyr-741) in the activation loop of DDR2 for phosphorylation. (korea.ac.kr)
The selectivity of an individual SH2 domain is not sharply defined, and a range of residues is typically tolerated at each site following the phosphotyrosine. (lu.se)
Residues from αB-helix and the EF and BG-loops are involved in binding of side chains C-terminal to phosphotyrosine in the ligand. (lu.se)
[8] Mutagenesis studies of type I IFNs, IFNAR1 and IFNAR2 demonstrated important binding residues, i.e. "hotspots", on the type I IFN subtypes which influenced its ability to bind to IFNAR2. (wikidoc.org)
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)
The APS SH2 dimer engages two kinase molecules, with pTyr-1158 of the kinase activation loop bound in the canonical phosphotyrosine binding pocket of the SH2 domain and a second phosphotyrosine, pTyr-1162, coordinated by two lysine residues in beta strand D. This structure provides a molecular visualization of one of the initial downstream recruitment events following insulin activation of its dimeric receptor. (rcsb.org)
Cytokine binding to the cell surface leads to phosphorylation of the receptor complex by receptor associated Janus kinases (JAKs) at tyrosine residues. (nature.com)
We identified a highly conserved, 13-residue segment (ADP-1) from adiponectin's collagen domain which comprises GXXG motifs and has one asparagine and two histidine residues that assist in oligomeric protein assembly. (phoenixpeptide.com)

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)
Thermodynamic measurements, structural determinations, and molecular computations were applied to a series of peptide ligands of the pp60(c-src) SH2 domain in an attempt to understand the critical binding determinants for this class of molecules. (rcsb.org)
Isothermal titration calorimetry (ITC) measurements were combined with structural data derived from X-ray crystallographic studies on 12 peptide-SH2 domain complexes. (rcsb.org)
The peptide ligands studied fall into two general classes: (1) dipeptides of the general framework N-acetylphosphotyrosine (or phosphotyrosine replacement)-Glu or methionine (or S-methylcysteine)-X, where X represents a hydrophobic amine, and (2) tetra- or pentapeptides of the general framework N-acetylphosphotyrosine-Glu-Glu-Ile-X, where X represents either Glu, Gln, or NH2. (rcsb.org)
Peptide ligands of pp60(c-src) SH2 domains: a thermodynamic and structural study. (weizmann.ac.il)
Recently the SH2 domains of Grb7 [22] and STAT3 STAT5 have already been targeted with peptides and peptide mimetics [23 24 Developing practical drugs concentrating on SH2 domains has significant problems. (biospraysehatalami.com)
PI3Kβ is synergistically activated by βγ subunit and phosphotyrosine-containing peptide [39]. (dpforex.com)
A collagen domain-derived short adiponectin peptide activates APPL1 and AMPK signaling pathways and improves glucose and fatty acid metabolisms. (phoenixpeptide.com)
Based on crystal structure of AdipoR1, we designed AdipoR1's peptide agonists using protein-peptide docking simulation and screened their receptor binding abilities and biological functions via surface plasmon resonance (SPR) and biological analysis. (phoenixpeptide.com)

A B-cell receptor is composed of a membrane-bound immunoglobulin molecule and a signal transduction moiety. (wikipedia.org)
A B cell is activated by its first encounter with an antigen (its "cognate antigen") that binds to its receptor, resulting in cell proliferation and differentiation to generate a population of antibody-secreting plasma B cells and memory B cells. (wikipedia.org)
The B-cell receptor is composed of two parts: A membrane-bound immunoglobulin molecule of one isotype (IgD, IgM, IgA, IgG, or IgE). (wikipedia.org)
BCRs have distinctive binding sites that rely on the complementarity of the surface of the epitope and the surface of the receptor, which often occurs by non-covalent forces. (wikipedia.org)
Results DIM, but not I3C, increased adipocyte differentiation through upregulation of peroxisome proliferator‐activated receptor γ and CCAAT/enhancer‐binding protein α. (researchgate.net)
The intracellular region contains the kinase domain sandwiched between the juxtamembrane domain used for docking insulin-receptor substrates (IRS), and the carboxy-terminal tail that contains two phosphotyrosine-binding sites. (rndsystems.com)
After synthesis, the single chain INS R precursor is glycosylated, dimerized and transported to the Golgi apparatus where it is processed at a furin-cleavage site within the middle fibronectin type III domain to generate the mature disulfide-linked alpha 2 beta 2 tetrameric receptor. (rndsystems.com)
Ligand binding induces a conformational change of the receptor, resulting in ATP binding, autophosphorylation, and subsequent downstream signaling. (rndsystems.com)
To the end, we examined receptor-bound immune system complexes (Body 4e) before and after ligand activation in GIV-depleted HeLa cells stably expressing little interfering RNA (siRNA)Cresistant, FLAG-tagged WT and mutant GIV (Supplemental Number S3, A and B). As demonstrated previously (Ghosh = 4). (bio-cavagnou.info)
GTP binding to SRP and SRP receptor is a prerequisite for SRP / SRP receptor complex formation. (mechanobio.info)
Alternative splicing of the avian trkB receptor generates an extracellular deletion (ED) isoform missing 11 amino acids from the neurotrophin-binding domain of the full-length (FL) receptor. (jneurosci.org)
Because of these profound effects on ligand specificity, reverse transcription-PCR was used to understand the expression of the FL and ED receptor isoforms at the level of single neurons. (jneurosci.org)
In this study, comparison of the ligand specificity of the full-length (FL) and ED receptor isoforms revealed that ED trkB exhibits a more restricted neurotrophin specificity than does FL trkB. (jneurosci.org)
DDR2 is a receptor tyrosine kinase whose activating ligands are various collagens. (korea.ac.kr)
Intro The kappa opioid receptor (KOR) and its endogenous ligand dynorphin are enriched in mind regions involved in stress response and potential medical energy for KOR antagonists (KORAn) offers been shown in major depression and substance abuse (Carroll and Carlezon 2013 JDTic is a potent and selective KORAn (Thomas 3 (50%) of the 6 subjects who received JDTic 1?mg. (sciencepop.org)
NMR structure of the interferon-binding ectodomain of the human interferon receptor. (wikidoc.org)
The interferon-α/β receptor (IFNAR) is a virtually ubiquitous membrane receptor which binds endogenous type I interferon (IFN) cytokines. (wikidoc.org)
Type I IFN receptor forms a ternary complex, composed of its two subunits IFNAR1 and IFNAR2, and a type I IFN ligand. (wikidoc.org)
Ligand binding to either subunit is required for and precedes dimerization and activation of the receptor. (wikidoc.org)
[7] Each type I IFN ligand contains a "hotspot", or a sequence of conserved amino acids that are involved in binding to the receptor, specifically the high affinity receptor IFNAR2, which determines the affinity of each ligand for the receptor. (wikidoc.org)
Structural analysis of type I IFN receptor with different type I IFN ligand subtypes revealed a similar binding site for the different agonists. (wikidoc.org)
[8] The evolutionary conservation of type I IFN subtypes binding the same IFNAR receptor at the same site with differing affinities suggests that type I IFNs are nonredundant and potentially regulate different cellular responses. (wikidoc.org)
The GDNF family ligands (GFLs) function through a glycosyl-phosphatidylinositol-(GPI) anchored coreceptor, GDNF family receptor alpha (GFRα), and rearranged during transfection (RET), a well-known receptor tyrosine kinase involved in kidney development, spermatogonial stem cell maintenance, and the development and maintenance of the sympathetic, parasympathetic, and enteric nervous systems [ 1 , 2 ]. (medsci.org)
When GFLs bind with GFRα, they form complexes and associate with the RET receptor, subsequently activating downstream signaling. (medsci.org)
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 interaction with the activated insulin receptor is mediated by the Src homology 2 (SH2) domain of APS. (rcsb.org)

1998). In both examples, the high affinity ligands can compete with the intramolecular interactions and release the catalytic domains for their in vivo targets. (lu.se)

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)
The VEE is a heterogeneous compartment containing the Adaptor Protein Phosphotyrosine Interacting with Pleckstrin homology Domain and Leucine Zipper 1 (APPL1) with distinct functions in regulating endosomal Gαs/cAMP signaling and rapid recycling. (frontiersin.org)
The tensin family member cten (C-terminal tensin like) is an Src homology 2 (SH2) and phosphotyrosine binding domain-containing focal adhesion molecule that may function as a tumor suppressor. (rupress.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)

Unexpectedly, the interaction between DLC-1 and the cten SH2 domain is independent of tyrosine phosphorylation of DLC-1. (rupress.org)
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)
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)
14). Ed, the ligand induces a close dimer formation of both the D1 and D2 domains separated by 39 Å, so that their intracellular regions become substrates for phosphorylation by two JAK2 molecules. (dpforex.com)

More analytically, the BCR complex consists of an antigen-binding subunit known as the membrane immunoglobulin (mIg), which is composed of two immunoglobulin light chains (IgLs) and two immunoglobulin heavy chains (IgHs) as well as two heterodimer subunits of Ig-α and Ig-β. (wikipedia.org)
The alpha subunit is localized extracellularly and mediates ligand binding while the transmembrane beta subunit contains the cytoplasmic kinase domain and mediates intracellular signaling. (rndsystems.com)
Each subunit of IFNAR contains an N-terminal ligand binding domain (with two or four fibronectin type II-like subdomains, for IFNAR2 and IFNAR1, respectively), a transmembrane (TM) domain, and a cytoplasmic domain. (wikidoc.org)

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)
These ligands, having multiple binding portions, may be expected to bind with high affinity and specificity. (elsevierpure.com)
a deletion in close proximity to this domain is likely to affect ligand specificity. (jneurosci.org)
and, various classes of phosphotyrosine-directed, phosphoserine- / phosphothreonine-directed, and dual-specificity phosphoprotein phosphatases that dephosphorylate activated MAPKs. (berkeley.edu)

Alternative splicing affects both the extracellular ligand-binding domains and the intracellular signal-transducing domains of the trks ( Barbacid, 1994 ). (jneurosci.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)
Phosphatase-resistant benzylmalonate and alpha,alpha-difluorobenzyl phosphonate analogs of phosphotyrosine retained some binding affinity for the pp60(c-src) SH2 domain but caused local structural perturbations in the phosphotyrosine-binding site. (rcsb.org)
1993). Based on these results, together with structural analyses of different ligand-binding models, it is apparent that SH2 domains bind distinct but overlapping sequence motifs. (lu.se)
Moreover, we find that Abl exerts its diverse activities through at least two different mechanisms: (1) a partly kinase-independent, structural function in midline attraction through its C-terminal F-actin binding domain (FABD) and (2) a kinase-dependent inhibition of repulsive guidance pathways that does not require the Abl C terminus. (silverchair.com)
[9] Importantly, structural studies have not revealed differences in ternary complex structures with IFNAR and various type I IFN subtypes, despite differences in ligand affinities. (wikidoc.org)

In vitro She binding assays demonstrate that phosphotyrosines resulting from DDR2 autophosphorylation are involved in Shc binding to the DDR2 cytosolic domain. (korea.ac.kr)
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)
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)

[7] [8] Upon binding of type I interferons, IFNAR activates the JAK-STAT signalling pathway , along with MAPK , PI3K , and Akt signaling pathways. (wikidoc.org)
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)
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)

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)
The phosphotyrosine residue continues to be estimated to supply one half from the binding energy of phosphopeptides towards the SH2 area [25]. (biospraysehatalami.com)

Yet, characterization of the emergence of differences in signaling events triggered by ligands with different affinities along the TCR signaling cascade remains incomplete. (nature.com)
The divergence between signals induced by ligands with different affinities occurred early in the canonical TCR signaling cascade. (nature.com)

3) DDR2 autophosphorylation generates cytosolic domain phosphotyrosines that promote the formation of DDR2 cytosolic domain-Shc signaling complexes. (korea.ac.kr)
In addition to their role in assembling activated complexes, particular SH2 domains also form intramolecular interactions that regulate enzyme activity. (lu.se)

In the canonical mode of SH2 binding, regions on either side of the central β sheet are involved in ligand binding. (eu.org)
It does so via a strong interaction (KD 1â µM) with a non-canonical binding site containing a structurally dynamic loop in CBP/p300 KIX. (bvsalud.org)

The structure reveals a novel dimeric configuration of the APS SH2 domain, wherein the C-terminal half of each protomer is structurally divergent from conventional, monomeric SH2 domains. (rcsb.org)

We also found that ADP-1 activates AMP-activated protein kinase (AMPK) in an adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper 1 (APPL1)-dependent pathway and stimulates glucose uptake in rat skeletal muscle cells (L-6 myotubes). (phoenixpeptide.com)

The screen for new phospho-tyrosine mimics binding to the SH2 domain of (pp60)src was initiated because of the limited cell penetration of phosphates. (rcsb.org)

4). Up coming we asked if the isolated SH2-like domain is enough for GIV to bind EGFR in cells. (bio-cavagnou.info)
Up coming we asked whether GIV's SH2-like domain is necessary for the recruitment of Gi3 to ligand-activated EGFR. (bio-cavagnou.info)
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)

Small differences in binding kinetics between TCR ligands lead to marked differences in T cell effector function and differentiation. (nature.com)
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)

We report that cten binds to another tumor suppressor, deleted in liver cancer 1 (DLC-1), and the SH2 domain of cten is responsible for the interaction. (rupress.org)
These results provide a novel mechanism whereby the SH2 domain of cten-mediated focal adhesion localization of DLC-1 plays an essential role in its tumor suppression activity. (rupress.org)

Based on the structure of whole Grb2, consolidated ligands were designed and synthesized. (elsevierpure.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)

Several different binding motifs are known, for example: pYEEI (Src-family SH2 domains), pY [IV]. (eu.org)
It contains Nterminalsites for myristylation and palmitylation, a PTK domain, and SH2 and SH3 domainswhich are involved in mediating protein-protein interactions with phosphotyrosine-containing andproline-rich motifs, respectively. (sciencepop.org)

The receptor's binding moiety is composed of a membrane-bound antibody that, like all antibodies, has two identical paratopes that are unique and randomly determined. (wikipedia.org)
Signal transduction moiety: a heterodimer called Ig-α/Ig-β (CD79), bound together by disulfide bridges. (wikipedia.org)
Normal mode calculations show that the dramatic decrease in entropy observed for the covalent thiohemiacetal complex is due to the inability of the phosphotyrosine moiety to transform lost rotational and translational degrees of freedom into new vibrational modes. (rcsb.org)

No correlation between affinity and fragment binding was found for these polar fragments and hence affinity-based screening would have overlooked some interesting starting points for inhibitor design. (rcsb.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)
In contrast, we were unable to identify electron density for hydrophobic fragments, confirming that hydrophobic interactions are important for inhibitor affinity but of minor importance for ligand recognition. (rcsb.org)

1998). The Src SH2 domain has been shown to bind a phosphorylated tyrosine at the C-terminus of the same molecule resulting inactivation of enzyme activity by rearrangement of catalytic center in the kinase domain (reviewed in Hubbard et al. (lu.se)

Low molecular weight (LMW) allosteric FSHR ligands were developed for use in assisted reproductive technology yet could also provide novel pharmacological tools to study FSHR. (frontiersin.org)

Non-phosphorylated peptides do not bind to the SH2 domains. (eu.org)

Point mutations cluster into the positively charged end of the molecule around the predicted binding site for phosphatidylinositol lipids. (embl.de)
Here, we construct a single-molecule electrical nanocircuit based on silicon nanowire field-effect transistors (SiNW-FETs) and functionalize it with an individual disordered c-Myc bHLH-LZ domain to enable label-free, in situ, and long-term measurements at the single-molecule level. (bvsalud.org)
A loop from the N-terminal SH2 domain binds to the catalytic cleft of the phosphatase domain in the same SHP-2 molecule leading to an autoinhibited configuration (Hof et al. (lu.se)

Our results suggest that a screening approach using protein crystallography is particularly useful to identify universal fragments for the conserved hydrophilic recognition sites found in target families such as SH2 domains, phosphatases, kinases, proteases, and esterases. (rcsb.org)

Val and Pro confer high-affinity binding at pY+3 - Ala and Ile are tolerated but confer weaker binding. (eu.org)
Ser, Thr, Asn and Ala are tolerated but confer weaker binding. (eu.org)

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

On the other hand, pulling forces delinks the antigen from the BCR, thus testing the quality of antigen binding. (wikipedia.org)

The interaction between SH2 domains and their substrates is however dependent also on cooperative contacts of other surface regions. (eu.org)
In this regard, the βI domain-dependent clustering of active β1 integrins is necessary to favor fibronectin-elicited directional EC motility, which cannot be effectively promoted by β1 integrin conformational activation alone. (life-science-alliance.org)
In this regard, we have recently shown that efficient activation of Ypk1 by TORC2 requires stimulation of TORC2 by the GTP-bound state of a Rab5 GTPase (Vps21/Ypt51) and that, in turn, Rab5-dependent endocytosis may be a mechanism to down-regulate TORC2 signaling after it has been activated. (berkeley.edu)

The large INS R extracellular domain is organized into two successive homologous globular domains, which are separated by a Cysteine-rich domain, followed by three fibronectin type III domains. (rndsystems.com)

Both the A and B isoforms bind insulin with high-affinity, but the A isoform has considerably higher affinity for IGF‑I and IGF-II. (rndsystems.com)
The predominant expression pattern of either FL or ED isoforms in single embryonic DRG neurons establishes the existence of two subpopulations exhibiting differential responsiveness to trkB ligands, indicating that regulated splicing of the extracellular domain of trkB may serve as a mechanism to restrict neuronal responsiveness to the neurotrophins. (jneurosci.org)

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)

Comparison of the X-ray structures shows that the presence of the H-bond acceptors and not their relative position within the pharmacophore are essential for fragment binding and/or high affinity binding of full length inhibitors. (rcsb.org)

Abl also regulates motor axon pathfinding through a non-overlapping set of functional domains. (silverchair.com)
The signal transducer and activator of transcription 5A (STAT5A) and STAT5B transcription factors have a conserved functional domain structure organized in N-terminal oligomerization, Coiled-coil, DNA-binding, Linker, SH2 and C-terminal transactivation domain. (nature.com)

These proof-of-concept results provide an understanding of the IDP-binding/folding mechanism and represent a promising nanotechnology for IDP conformation/interaction studies and drug discovery. (bvsalud.org)

Manifestation of the SH2-lacking GIV mutant (Arg 1745Leu) that cannot bind RTKs impaired all previously shown features of GIVAkt improvement, actin redesigning, and cell migration. (bio-cavagnou.info)

After binding its hormone FSH, FSHR undergoes internalization to very early endosomes (VEEs) for its acute signaling and sorting to a rapid recycling pathway. (frontiersin.org)

PSPN not only binds GFRα4 but also signals in neurons mediated by GFRα1 [ 5 ]. (medsci.org)

By exploiting four monoclonal antibodies recognizing distinct conformational epitopes, we show that in endothelial cells (ECs), the extracellular βI domain, but not the hybrid or I-EGF2 domain of active β1 integrins, promotes their FAK-regulated clustering into tensin 1-containing fibrillar adhesions and impairs their endocytosis. (life-science-alliance.org)

Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. (embl.de)
Mutations in the tyrosine kinase, whether in BCR-ABL in CML or a FLT3 mutation in AML, bypass control that comes from ligand binding. (shu.edu)

The many processes involving SH2 domains range from mitogenic signaling to T cell activation. (eu.org)
The kinetic proofreading model postulates that TCR ligand discrimination is due to several signaling steps that introduce a delay between ligand binding and T cell activation. (nature.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)

Within this review we will discuss initiatives to develop agencies that focus on SH2 domains which have been examined in breast cancers versions. (biospraysehatalami.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)

Anatomy20

Organisms12

Diseases1

Chemicals and Drugs116

Analytical, Diagnostic and Therapeutic Techniques and Equipment33

Phenomena and Processes72

Information Science4

Health Care1

Receptors16

Proteins26

Residues14

Peptide9

Receptor29

High affinity ligands1

Homology5

Phosphorylation5

Subunit3

Specificity4

Intracellular1

Structural5

Assays3

Pathways4

Residue2

Affinities2

Complexes2

Canonical2

Structurally1

Adaptor protein1

Pp601

EGFR5

Kinetics2

Tumor2

GRB21

Endogenous1

Motifs2

Moiety3

Affinity-based1

Interactions2

Kinase domain1

Allosteric1

Peptides1

Molecule3

Phosphatases1

Confer2

Effector1

Antigen1

Dependent3

Fibronectin type1

Isoforms2

Molecular2

Inhibitors1

Functional2

Interaction1

RTKs1

Internalization1

Signals1

Promotes1

Mutations2

Activation3

Cancers1

Modular1