Abstract
We performed GST pull-down assay using the SH2 domain of Nck1 as bait. The resulting precipitates were separated by 2-DE. Mass spectrometry analysis revealed a group of Nck1 SH2 domain-binding proteins that were differentially expressed in HCC. One of these proteins, dermcidin (DCD), and its interac...
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PMID: 21397687
PDF is available here.
Abstract
We show that the protein folding flows can be surprisingly similar to turbulent fluid flows. Studying a benchmark model protein (an SH3 domain), we have found that the flows for the slow folding trajectories of the protein, in which a partly formed N- and C-terminal β sheet hinders the RT loop from...
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PMID: 21405726
PDF is available here.
Abstract
SH3 is a ubiquitous domain mediating protein-protein interactions. Recent solution NMR structural studies have shown that a proline-rich peptide is capable of binding to the human vinexin SH3 domain. Here, an orthogonal amber tRNA/tRNA synthetase pair for (15)N/(19)F-trifluoromethyl-phenylalanine ((...
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PMID: 20946873
PDF is available here.
Daniel W Sherbenou,
Oliver Hantschel,
Ines Kaupe,
Stephanie Willis,
Thomas Bumm,
Lalita P Turaga,
Thoralf Lange,
Kim-Hien Dao,
Richard D Press,
Brian J Druker,
Giulio Superti-Furga and
Michael W Deininger
Abstract
We screened for such mutations in a cohort of consecutive CML patients with various levels of response. Regulatory domain mutations were detected in 7 of 98 patients, whereas kinase domain mutations were detected in 29. One mutation (T212R) conferred in vitro tyrosine kinase inhibitor resistance and...
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PMID: 20519627
PDF is available here.
Abstract
The potential usefulness of artificially selected peptides as probes to detect specific proteins has been proposed because of the ease and low cost of syntheses, manipulation, and genetic expression. However, the affinities of these peptides to their target proteins are generally too low to be pract...
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PMID: 20510935
PDF is available here.
Abstract
We report that the fourth Shc family member, ShcD, associates with TrkB receptor and regulates BDNF-induced MAPK activation. Yeast two-hybrid assay and Co-IP experiments demonstrate ShcD interacts with TrkB in a kinase-activity-dependent manner. Confocal analysis shows ShcD cololizes well with TrkB...
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PMID: 20663410
PDF is available here.
Abstract
We mutated the amino acid residues forming the contacts between the SH2 domain and the beta3-alphaC loop. The mutation of the beta3-alphaC loop Ala228 to glycine and of the SH2 domain Tyr116, Tyr133, Leu138, and Leu149 to alanine resulted in the inability of the SH2 domain ligand to activate Csk. Fu...
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PMID: 20434462
PDF is available here.
Abstract
Our NMR studies showed that residues with high average area buried upon folding (AABUF) parameter collapsed to form the clusters. Interestingly, the hydrophobic collapses were not stabilized by long-range tertiary interactions among the clusters that were typically observed in non-amyloidogenic unfo...
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PMID: 20438713
PDF is available here.
Abstract
We show that anti-CD3 induced ZAP-70 cluster formation is significantly reduced in the absence of SLP-76 (i.e., J14 cells) and in the presence of a mutant of SLP-76 (4KE) in Jurkat and primary T cells. Both the number of cells with clusters and the number of clusters per cell were reduced. This effe...
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PMID: 20534575
PDF is available here.
Abstract
A multi-scale parameterization approach, factor analysis scales of generalized amino acid information combined with auto cross covariance, was used to develop quantitative sequence-activity models of peptides using support vector machines. The results demonstrated that this approach could well chara...
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PMID: 20443765
PDF is available here.
Abstract
HNCO/HNCACO type correlation experiments are an alternative for assignment of backbone resonances in extensively deuterated proteins in the solid-state, given the fact that line widths on the order of 14-17 Hz are achieved in the carbonyl dimension without the need of high power decoupling. The achi...
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PMID: 20232230
PDF is available here.
Abstract
Understanding how proteins adopt their unique native structures requires a complete structural characterization of the rate-limiting transition state(s) along the folding pathway. By definition, transition states are not significantly populated and are only accessible via folding kinetics studies. I...
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PMID: 20453926
PDF is available here.
Abstract
We employed this approach, coupled with partial least square (PLS) regression and genetic algorithm (GA), to predict and to interpret the peptide-binding behavior to SH3 domain. In comparison with the previous works, our method is more capable of capturing important factors in the SH3 domain-peptide...
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PMID: 19669081
PDF is available here.
Abstract
The protein p104 was first isolated as a binding partner of the Src homology domain of phospholipase Cgamma1, and has been shown to associate with p85alpha, Grb2. The ectopic expression of p104 reduced cellular growth rate, which was also achieved with the overexpression of only the proline-rich reg...
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PMID: 20356461
PDF is available here.
Abstract
We first attempted to investigate the SH3BP2 gene in peripheral giant cell lesion (PGCL). The effect of SH3BP2 gene mutations on the transcription of the downstream genes nuclear factor of activated T cells (NFATc1) and the cytokine tumor necrosis factor-alpha (TNF-alpha) was also investigated toget...
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PMID: 20002873
PDF is available here.
Abstract
We report the first application of coordination complexes as functional proteomimetics of the Src homology 2 (SH2) phosphopeptide-binding domain. As a proof-of-concept, functionalized bis-dipicolylamine (BDPA) copper(ii) complexes are shown to disrupt oncogenic Stat3-Stat3 protein complexes and elic...
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PMID: 20107641
PDF is available here.
Abstract
We demonstrate that the SH3 domain functions to localize IRSp53 to lamellipodia and that IRSp53 mutated in its SH3 domain fails to induce filopodia. Through SH3 domain-swapping experiments, we show that the related IRTKS SH3 domain is not functional in lamellipodial localization. IRSp53 binds to 14-...
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PMID: 19933840
PDF is available here.
Abstract
We identified conserved structural features in the loops of SH2 domains responsible for controlling access to these surface pockets. We engineered new loops in an SH2 domain that altered specificity as predicted. Thus, selective blockage of binding subsites or pockets by surface loops provides a mol...
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PMID: 20442417
PDF is available here.
Abstract
Protein SHA-D of "SH3-Bergerac" chimeric proteins family was constructed by substitution of beta-turn N47-D48 in spectrin SH3-domain by KATANDKTYE amino acid sequence. Structural and dynamics properties of SHA-D in solution were studied by with the help of high-resolution NMR. The extension of SHA-D...
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PMID: 20823919
PDF is available here.
Abstract
We have developed multiple stable cell lines containing subgenomic HCV RNA that are resistant to treatment with interferon alpha (IFN-α. Characterization of these IFN-α resistant replicon cells showed defects in the phosphorylation and nuclear translocation of STAT1 and STAT2 proteins due to a def...
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PMID: 20949125
PDF is available here.
Abstract
Src family tyrosine kinases (SFKs) play key roles in regulating signal transduction in cellular processes. However, hyper-activated SFKs lead to uncontrolled cell proliferation and cancers. For both Src SH2 and SH3 domains involve in the regulation of tumorigenesis signal pathways, the SH2 and SH3 i...
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PMID: 20158477
PDF is available here.
Walter H A WH Kahr,
Anna A Savoia,
Fred G FG Pluthero,
Ling L Li,
Hilary H Christensen,
Daniela D De Rocco,
Chanchai C Traivaree,
Sheila E SE Butchart,
Julie J Curtin,
Elliott J EJ Stollar,
Julie D JD Forman-Kay and
Victor S VS Blanchette
Abstract
We describe a patient with a Trp33Cys missense mutation in the SH3-like domain of MHC-IIA. Abnormal platelet function was observed using platelet aggregometry with the agonists epinephrine and adenosine diphosphate (ADP). Patient granulocytes and megakaryocytes, but not platelets, contained abnormal...
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PMID: 19967157
PDF is available here.
Abstract
Our hypothesis was that TSP-1-induced VSMC migration is dependent on the CD44 receptor, and that HyA and TSP-1 share migratory signaling pathways....
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PMID: 19887196
PDF is available here.
Abstract
We are targeting its SH2 domain to prevent docking to cytokine and growth factor receptors and subsequent signaling. One of the important elements of the recognition sequence, pTyr-Xxx-Xxx-Gln, is glutamine. We incorporated novel Gln mimics into a lead peptide, pCinn-Leu-Pro-Gln-NHBn, and found that...
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PMID: 19728728
PDF is available here.
Abstract
We show that the presence of paramagnetic compounds in the bulk solvent induces a site-specific relaxation in addition to local dynamics, which is dependent on the surface accessibility of the respective amide proton in the protein. Differentiation between paramagnetic relaxation and dynamics was ac...
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PMID: 19736939
PDF is available here.
Abstract
We present evidence of distinct STI571-induced modulation of abl functions using high-resolution live-cell imaging approaches. Within lamellipodia of fibroblast cells, STI571 was found to induce rapid translocation of abl to the lamellipodium tip. Quantitative analysis yielded 0.81 {micro}M and 1.8...
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PMID: 18835981
PDF is available here.
Abstract
We describe a relaxation dispersion method for measuring site-specific motional parameters of methyl containing residues in the excited state. The approach is applied to the invisible unfolded state of the G48M Fyn SH3 domain that is in exchange with the folded conformation. Not surprisingly, the de...
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PMID: 19685870
PDF is available here.
Abstract
We present a site-resolved study of slow (ms to s) motions in a protein in the solid (microcrystalline) state performed with the use of a modified version of the centerband-only detection of exchange (CODEX) NMR experiment. CODEX was originally based on measuring changes in molecular orientation by...
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PMID: 19673476
PDF is available here.
Abstract
We present an experimental method for establishing the relative orientations of methyl groups in invisible, excited states of proteins by measuring methyl (1)H-(13)C residual dipolar couplings (RDCs). In our approach, four two-dimensional spectra are acquired at a pair of static magnetic fields. Eac...
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PMID: 19627152
PDF is available here.
Abstract
We report the isolation and functional characterization of five new CLE genes from the potato cyst nematode Globodera rostochiensis. Unlike typical plant CLE peptides that contain a single CLE motif, four of the five Gr-CLE genes encode CLE proteins with multiple CLE motifs. These Gr-CLE genes were...
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PMID: 19656047
PDF is available here.
Abstract
The synthesis of prodrugs targeted to the SH2 domain of Stat3 is reported. Using a convergent strategy, the pivaloyloxymethyl phosphonodiester of pentachlorophenyl 4-phosphonodifluoromethylcinnamate, a phosphotyrosine surrogate, was synthesized and used to acylate peptidomimetic fragments that were...
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PMID: 19594124
PDF is available here.
Abstract
Phosphopeptide pTyr-Glu-Glu-Ile (pYEEI) has been introduced as an optimal Src SH2 domain ligand. Peptides, Ac-K(IDA)pYEEIEK(IDA) (1), Ac-KpYEEIEK (2), Ac-K(IDA)pYEEIEK (3), and Ac-KpYEEIEK(IDA) (4), containing 0-2 iminodiacetate (IDA) groups at the N- and C-terminal lysine residues were synthesized...
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PMID: 19539345
PDF is available here.
Abstract
We investigated, side by side, the roles of Nckalpha and Nckbeta in PDGF-BB-stimulated DF migration. We found that cells expressing the PDGFRbeta-Y751F mutant (preventing Nckalpha binding) or PDGFRbeta-Y1009F mutant (preventing Nckbeta binding), DF cells isolated from Nckalpha- or Nckbeta-knockout m...
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PMID: 19242519
PDF is available here.
Abstract
We show that Src phosphorylates Tks5 at Y557, inducing it to associate directly with the SH3-SH2 domain adaptor proteins Nck1 and Nck2 in invadopodia. Tks5 mutants unable to bind Nck show reduced matrix degradation-promoting activity and recruit actin to invadopodia inefficiently. Conversely, Src- a...
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PMID: 19596797
PDF is available here.
Abstract
We focus on a novel protein, GAREM (Grb2-associated and regulator of Erk/MAPK) as a downstream molecule of the EGF receptor. GAREM is phosphorylated at tyrosine 105 and 453 after EGF stimulation. Grb2 was identified as its binding partner, and the proline-rich motifs of GAREM are recognized by the N...
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PMID: 19509291
PDF is available here.
Abstract
We tested to see whether the activity of SHIP1 was regulated via phos pho ryl a tion with PKA. We prepared pure recombinant SHIP1 from HEK-293 cells and found it can be rapidly phos pho ryl a ted by PKA to a stoichiometry of 0.6 mol of PO(4)/mol of SHIP1. In (32)P-labeled HEK-293 cells transfected w...
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PMID: 19494109
PDF is available here.
Abstract
We conducted a yeast two-hybrid screen to identify molecules that physically interact with Eph receptors using the cytoplasmic domain of EphA3 as "bait". This study identified Nck1 as a strong binding partner of EphA3 as assayed using both GST fusion protein pull down and co-immunoprecipitation tech...
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PMID: 19505147
PDF is available here.
Abstract
We have examined the role of PCH family proteins, Nwk/Bzz1p-like protein (NLP) and Syndapin-like protein (SLP), in the regulation of the formation and trafficking of WASP-vesicles during chemotaxis. NLP and SLP appear to be functionally redundant and deletion of both nlp and slp genes causes the los...
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PMID: 19409937
PDF is available here.
Abstract
We showed that Abl kinases (c-Abl, Arg) are activated downstream of PDGF in a manner dependent on Src kinases and PLC-gamma1, and promote PDGF-mediated proliferation and migration of fibroblasts. We additionally demonstrated that Abl kinases bind directly to PDGFR-beta via their SH2 domains.In this...
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PMID: 19275932
PDF is available here.
Abstract
We investigated the structural underpinnings of this intramolecular coupling and found that in addition to a previously described SH3 domain beta strand, two structural elements are crucial for maintaining a strong and yet potentially modifiable SH3-GK intramolecular coupling: an intrinsically weak...
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PMID: 19427861
PDF is available here.
Abstract
We investigated the structural underpinnings of this intramolecular coupling and found that in addition to a previously described SH3 domain beta strand, two structural elements are crucial for maintaining a strong and yet potentially modifiable SH3-GK intramolecular coupling: an intrinsically weak...
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PMID: 19427861
PDF is available here.
Abstract
We investigated the structural underpinnings of this intramolecular coupling and found that in addition to a previously described SH3 domain beta strand, two structural elements are crucial for maintaining a strong and yet potentially modifiable SH3-GK intramolecular coupling: an intrinsically weak...
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PMID: 19427861
PDF is available here.
Abstract
We investigated the structural underpinnings of this intramolecular coupling and found that in addition to a previously described SH3 domain beta strand, two structural elements are crucial for maintaining a strong and yet potentially modifiable SH3-GK intramolecular coupling: an intrinsically weak...
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PMID: 19427861
PDF is available here.
Abstract
We investigated the structural underpinnings of this intramolecular coupling and found that in addition to a previously described SH3 domain beta strand, two structural elements are crucial for maintaining a strong and yet potentially modifiable SH3-GK intramolecular coupling: an intrinsically weak...
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PMID: 19427861
PDF is available here.
Abstract
We investigated the structural underpinnings of this intramolecular coupling and found that in addition to a previously described SH3 domain beta strand, two structural elements are crucial for maintaining a strong and yet potentially modifiable SH3-GK intramolecular coupling: an intrinsically weak...
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PMID: 19427861
PDF is available here.
Abstract
We investigated the structural underpinnings of this intramolecular coupling and found that in addition to a previously described SH3 domain beta strand, two structural elements are crucial for maintaining a strong and yet potentially modifiable SH3-GK intramolecular coupling: an intrinsically weak...
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PMID: 19427861
PDF is available here.
Abstract
We investigated the structural underpinnings of this intramolecular coupling and found that in addition to a previously described SH3 domain beta strand, two structural elements are crucial for maintaining a strong and yet potentially modifiable SH3-GK intramolecular coupling: an intrinsically weak...
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PMID: 19427861
PDF is available here.
Abstract
We investigated the structural underpinnings of this intramolecular coupling and found that in addition to a previously described SH3 domain beta strand, two structural elements are crucial for maintaining a strong and yet potentially modifiable SH3-GK intramolecular coupling: an intrinsically weak...
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PMID: 19427861
PDF is available here.
Abstract
We investigated the structural underpinnings of this intramolecular coupling and found that in addition to a previously described SH3 domain beta strand, two structural elements are crucial for maintaining a strong and yet potentially modifiable SH3-GK intramolecular coupling: an intrinsically weak...
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PMID: 19427861
PDF is available here.
Abstract
We investigated the structural underpinnings of this intramolecular coupling and found that in addition to a previously described SH3 domain beta strand, two structural elements are crucial for maintaining a strong and yet potentially modifiable SH3-GK intramolecular coupling: an intrinsically weak...
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PMID: 19427861
PDF is available here.
Abstract
We investigated the structural underpinnings of this intramolecular coupling and found that in addition to a previously described SH3 domain beta strand, two structural elements are crucial for maintaining a strong and yet potentially modifiable SH3-GK intramolecular coupling: an intrinsically weak...
|
PMID: 19427861
PDF is available here.
Abstract
We investigated the structural underpinnings of this intramolecular coupling and found that in addition to a previously described SH3 domain beta strand, two structural elements are crucial for maintaining a strong and yet potentially modifiable SH3-GK intramolecular coupling: an intrinsically weak...
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PMID: 19427861
PDF is available here.
Abstract
We investigated the structural underpinnings of this intramolecular coupling and found that in addition to a previously described SH3 domain beta strand, two structural elements are crucial for maintaining a strong and yet potentially modifiable SH3-GK intramolecular coupling: an intrinsically weak...
|
PMID: 19427861
PDF is available here.
Abstract
We investigated the structural underpinnings of this intramolecular coupling and found that in addition to a previously described SH3 domain beta strand, two structural elements are crucial for maintaining a strong and yet potentially modifiable SH3-GK intramolecular coupling: an intrinsically weak...
|
PMID: 19427861
PDF is available here.
Abstract
We investigated the structural underpinnings of this intramolecular coupling and found that in addition to a previously described SH3 domain beta strand, two structural elements are crucial for maintaining a strong and yet potentially modifiable SH3-GK intramolecular coupling: an intrinsically weak...
|
PMID: 19427861
PDF is available here.
Abstract
We investigated the structural underpinnings of this intramolecular coupling and found that in addition to a previously described SH3 domain beta strand, two structural elements are crucial for maintaining a strong and yet potentially modifiable SH3-GK intramolecular coupling: an intrinsically weak...
|
PMID: 19427861
PDF is available here.
Abstract
We investigated the structural underpinnings of this intramolecular coupling and found that in addition to a previously described SH3 domain beta strand, two structural elements are crucial for maintaining a strong and yet potentially modifiable SH3-GK intramolecular coupling: an intrinsically weak...
|
PMID: 19427861
PDF is available here.
Abstract
We investigated the structural underpinnings of this intramolecular coupling and found that in addition to a previously described SH3 domain beta strand, two structural elements are crucial for maintaining a strong and yet potentially modifiable SH3-GK intramolecular coupling: an intrinsically weak...
|
PMID: 19427861
PDF is available here.
Abstract
We investigated the structural underpinnings of this intramolecular coupling and found that in addition to a previously described SH3 domain beta strand, two structural elements are crucial for maintaining a strong and yet potentially modifiable SH3-GK intramolecular coupling: an intrinsically weak...
|
PMID: 19427861
PDF is available here.