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Article ; Online: Structural systems biology and multiscale signaling models.

Telesco, Shannon E / Radhakrishnan, Ravi

2012 Volume 40, Issue 11, Page(s) 2295–2306

Abstract: We review current advances in experimental as well as computational modeling and simulation approaches to structural systems biology, whose overall aim is to build quantitative models of signaling networks while retaining the crucial elements of ... ...

Abstract	We review current advances in experimental as well as computational modeling and simulation approaches to structural systems biology, whose overall aim is to build quantitative models of signaling networks while retaining the crucial elements of molecular specificity. We briefly discuss the current and emerging experimental and computational methods, particularly focusing on hybrid and multiscale methods, and highlight several applications in cell signaling with quantitative and predictive capabilities. The scope of such models range from delineating protein-protein interactions to describing clinical implications.
MeSH term(s)	Computer Simulation ; Humans ; Models, Biological ; Signal Transduction ; Systems Biology/methods
Language	English
Publishing date	2012-04-27
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. ; Review
ZDB-ID	185984-5
ISSN	1573-9686 ; 0191-5649 ; 0090-6964
ISSN (online)	1573-9686
ISSN	0191-5649 ; 0090-6964
DOI	10.1007/s10439-012-0576-6
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Article ; Online: Molecular modeling of ErbB4/HER4 kinase in the context of the HER4 signaling network helps rationalize the effects of clinically identified HER4 somatic mutations on the cell phenotype.

Telesco, Shannon E / Vadigepalli, Rajanikanth / Radhakrishnan, Ravi

Biotechnology journal

2013 Volume 8, Issue 12, Page(s) 1452–1464

Abstract: In the ErbB/HER family of receptor tyrosine kinases, the deregulation of the EGFR/ErbB1/HER1, HER2/ErbB2, and HER3/ErbB3 kinases is associated with several cancers, while the HER4/ErbB4 kinase has been shown to play an anti-carcinogenic role in certain ... ...

Abstract	In the ErbB/HER family of receptor tyrosine kinases, the deregulation of the EGFR/ErbB1/HER1, HER2/ErbB2, and HER3/ErbB3 kinases is associated with several cancers, while the HER4/ErbB4 kinase has been shown to play an anti-carcinogenic role in certain tumors. We present molecular and network models of HER4/ErbB4 activation and signaling in order to elucidate molecular mechanisms of activation and rationalize the effects of the clinically identified HER4 somatic mutants. Our molecular-scale simulations identify the important role played by the interactions within the juxtamembrane region during the activation process. Our results also support the hypothesis that the HER4 mutants may heterodimerize but not activate, resulting in blockage of the HER4-STAT5 differentiation pathway, in favor of the proliferative PI3K/AKT pathway. Translating our molecular simulation results into a cellular pathway model of wild type versus mutant HER4 signaling, we are able to recapitulate the major features of the PI3K/AKT and JAK/STAT activation downstream of HER4. Our model predicts that the signaling downstream of the wild type HER4 is enriched for the JAK-STAT pathway, whereas downstream of the mutant HER4 is enriched for the PI3K/AKT pathway. HER4 mutations may hence constitute a cellular shift from a program of differentiation to that of proliferation.
MeSH term(s)	Computational Biology/methods ; ErbB Receptors/chemistry ; ErbB Receptors/genetics ; ErbB Receptors/metabolism ; Humans ; Models, Biological ; Molecular Dynamics Simulation ; Mutation ; Protein Subunits/chemistry ; Protein Subunits/genetics ; Protein Subunits/metabolism ; Receptor, ErbB-4 ; Signal Transduction/genetics ; Signal Transduction/physiology
Chemical Substances	Protein Subunits ; ERBB4 protein, human (EC 2.7.10.1) ; ErbB Receptors (EC 2.7.10.1) ; Receptor, ErbB-4 (EC 2.7.10.1)
Language	English
Publishing date	2013-12-04
Publishing country	Germany
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2221885-3
ISSN	1860-7314 ; 1860-6768
ISSN (online)	1860-7314
ISSN	1860-6768
DOI	10.1002/biot.201300022
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Article ; Online: Atomistic insights into regulatory mechanisms of the HER2 tyrosine kinase domain: a molecular dynamics study.

Telesco, Shannon E / Radhakrishnan, Ravi

Biophysical journal

2009 Volume 96, Issue 6, Page(s) 2321–2334

Abstract: HER2 (ErbB2/Neu) is a receptor tyrosine kinase belonging to the epidermal growth factor receptor (EGFR)/ErbB family and is overexpressed in 20-30% of human breast cancers. Although several crystal structures of ErbB kinases have been solved, the precise ... ...

Abstract	HER2 (ErbB2/Neu) is a receptor tyrosine kinase belonging to the epidermal growth factor receptor (EGFR)/ErbB family and is overexpressed in 20-30% of human breast cancers. Although several crystal structures of ErbB kinases have been solved, the precise mechanism of HER2 activation remains unknown, and it has been suggested that HER2 is unique in its requirement for phosphorylation of Y877, a key tyrosine residue located in the activation loop. To elucidate mechanistic details of kinase domain regulation, we performed molecular dynamics simulations of a homology-modeled HER2 kinase structure in active and inactive conformations. Principal component analysis of the atomistic fluctuations reveals a tight coupling between the activation loop and catalytic loop that may contribute to alignment of residues required for catalysis in the active kinase. The free energy perturbation method is also employed to predict a role for phosphorylated Y877 in stabilizing the kinase conformations. Finally, simulation results are presented for a HER2/EGFR heterodimer and reveal that the dimeric interface induces a rearrangement of the alphaC helix toward the active conformation. Elucidation of the molecular regulatory mechanisms in HER2 will help establish structure-function relationships in the wild-type kinase, as well as predict mutations with a propensity for constitutive activation in HER2-mediated cancers.
MeSH term(s)	Algorithms ; Computer Simulation ; Databases, Protein ; ErbB Receptors/chemistry ; Hydrogen Bonding ; Hydrophobic and Hydrophilic Interactions ; Models, Molecular ; Molecular Sequence Data ; Phosphorylation ; Principal Component Analysis ; Protein Stability ; Protein Structure, Secondary ; Receptor, ErbB-2/chemistry ; Receptor, ErbB-4
Chemical Substances	ERBB4 protein, human (EC 2.7.10.1) ; ErbB Receptors (EC 2.7.10.1) ; Receptor, ErbB-2 (EC 2.7.10.1) ; Receptor, ErbB-4 (EC 2.7.10.1)
Language	English
Publishing date	2009-03-16
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	218078-9
ISSN	1542-0086 ; 0006-3495
ISSN (online)	1542-0086
ISSN	0006-3495
DOI	10.1016/j.bpj.2008.12.3912
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Article ; Online: Fecal Microbiota Signatures Are Associated with Response to Ustekinumab Therapy among Crohn's Disease Patients.

Doherty, Matthew K / Ding, Tao / Koumpouras, Charlie / Telesco, Shannon E / Monast, Calixte / Das, Anuk / Brodmerkel, Carrie / Schloss, Patrick D

mBio

2018 Volume 9, Issue 2

Abstract: The fecal microbiota is a rich source of biomarkers that have previously been shown to be predictive of numerous disease states. Less well studied is the effect of immunomodulatory therapy on the microbiota and its role in response to therapy. This study ...

Abstract	The fecal microbiota is a rich source of biomarkers that have previously been shown to be predictive of numerous disease states. Less well studied is the effect of immunomodulatory therapy on the microbiota and its role in response to therapy. This study explored associations between the fecal microbiota and therapeutic response of Crohn's disease (CD) patients treated with ustekinumab (UST; Stelara) in the phase 2 CERTIFI study. Using stool samples collected over the course of 22 weeks, the composition of these subjects' fecal bacterial communities was characterized by sequencing the 16S rRNA gene. Subjects in remission could be distinguished from those with active disease 6 weeks after treatment using random forest models trained on subjects' baseline microbiota and clinical data (area under the curve [AUC] of 0.844, specificity of 0.831, sensitivity of 0.774). The most predictive operational taxonomic units (OTUs) that were ubiquitous among subjects were affiliated with
MeSH term(s)	Adult ; Bacteria/classification ; Bacteria/genetics ; Bacteria/isolation & purification ; Clinical Trials, Phase II as Topic ; Crohn Disease/drug therapy ; DNA, Bacterial/chemistry ; DNA, Bacterial/genetics ; DNA, Ribosomal/chemistry ; DNA, Ribosomal/genetics ; Feces/microbiology ; Female ; Gastrointestinal Microbiome ; Humans ; Immunologic Factors/administration & dosage ; Male ; Microbiota ; Middle Aged ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Treatment Outcome ; Ustekinumab/administration & dosage
Chemical Substances	DNA, Bacterial ; DNA, Ribosomal ; Immunologic Factors ; RNA, Ribosomal, 16S ; Ustekinumab (FU77B4U5Z0)
Language	English
Publishing date	2018-03-13
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2557172-2
ISSN	2150-7511 ; 2161-2129
ISSN (online)	2150-7511
ISSN	2161-2129
DOI	10.1128/mBio.02120-17
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Article: Investigating Molecular Mechanisms of Activation and Mutation of the HER2 Receptor Tyrosine Kinase through Computational Modeling and Simulation.

Telesco, Shannon E / Shih, Andrew / Liu, Yingting / Radhakrishnan, Ravi

Cancer research journal

2014 Volume 4, Issue 4, Page(s) 1–35

Abstract: Human epidermal growth factor receptor 2 (HER2)/ErbB2 is a receptor tyrosine kinase belonging to the EGFR/ErbB family and is overexpressed in 20-30% of human breast cancers. Since there is a growing effort to develop pharmacological inhibitors of the ... ...

Abstract	Human epidermal growth factor receptor 2 (HER2)/ErbB2 is a receptor tyrosine kinase belonging to the EGFR/ErbB family and is overexpressed in 20-30% of human breast cancers. Since there is a growing effort to develop pharmacological inhibitors of the HER2 kinase for the treatment of breast cancer, it is clinically valuable to rationalize how specific mutations impact the molecular mechanism of receptor activation. Although several crystal structures of the ErbB kinases have been solved, the precise mechanism of HER2 activation remains unknown, and it has been suggested that HER2 is unique in its requirement for phosphorylation of Y877, a key tyrosine residue located in the activation loop (A-loop). In our studies, discussed here, we have investigated the mechanisms that are important in HER2 kinase domain regulation and compared them with the other ErbB family members, namely EGFR and ErbB4, to determine the molecular basis for HER2's unique mode of activation. We apply computational simulation techniques at the atomic level and at the electronic structure (quantum mechanical) level to elucidate details of the mechanisms governing the kinase domains of these ErbB members. Through analysis of our simulation results, we have discovered potential regulatory mechanisms common to EGFR, HER2, and ErbB4, including a tight coupling between the A-loop and catalytic loop that may contribute to alignment of residues required for catalysis in the active kinase. We further postulate an autoinhibitory mechanism whereby the inactive kinase is stabilized through sequestration of catalytic residues. In HER2, we also predict a role for phosphorylated Y877 in bridging a network of hydrogen bonds that fasten the A-loop in its active conformation, suggesting that HER2 may be unique among the ErbB members in requiring A-loop tyrosine phosphorylation for functionality. In EGFR, HER2, and ErbB4, we discuss the possible effects of activating mutations. Delineation of the activation mechanism of HER2 in the context of the other ErbB members is crucial for understanding how the activated kinase might interact with downstream molecules and couple to signaling cascades that promote cancer. Our comparative analysis furthers insight into the mechanics of activation of the HER2 kinase and enables us to predict the effect of an identified insertion mutation on HER2 activation. Further understanding of the mechanism of HER2 kinase activation at the atomic scale and how it couples to downstream signaling at the cellular scale will elucidate predictive molecular phenotypes that may indicate likelihood of response to specific therapies for HER2-mediated cancers.
Language	English
Publishing date	2014-04-02
Publishing country	United States
Document type	Journal Article
ISSN	1935-2506
ISSN	1935-2506
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Article: Analysis of Somatic Mutations in Cancer: Molecular Mechanisms of Activation in the ErbB Family of Receptor Tyrosine Kinases.

Shih, Andrew J / Telesco, Shannon E / Radhakrishnan, Ravi

Cancers

2011 Volume 3, Issue 1, Page(s) 1195–1231

Abstract: The ErbB/EGFR/HER family of kinases consists of four homologous receptor tyrosine kinases which are important regulatory elements in many cellular processes, including cell proliferation, differentiation, and migration. Somatic mutations in, or over- ... ...

Abstract	The ErbB/EGFR/HER family of kinases consists of four homologous receptor tyrosine kinases which are important regulatory elements in many cellular processes, including cell proliferation, differentiation, and migration. Somatic mutations in, or over-expression of, the ErbB family is found in many cancers and is correlated with a poor prognosis; particularly, clinically identified mutations found in non-small-cell lung cancer (NSCLC) of ErbB1 have been shown to increase its basal kinase activity and patients carrying these mutations respond remarkably to the small tyrosine kinase inhibitor gefitinib. Here, we analyze the potential effects of the currently catalogued clinically identified mutations in the ErbB family kinase domains on the molecular mechanisms of kinase activation. Recently, we identified conserved networks of hydrophilic and hydrophobic interactions characteristic to the active and inactive conformation, respectively. Here, we show that the clinically identified mutants influence the kinase activity in distinctive fashion by affecting the characteristic interaction networks.
Language	English
Publishing date	2011-06-16
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers3011195
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Article ; Online: Cohort profile of the PRoteomic Evaluation and Discovery in an IBD Cohort of Tri-service Subjects (PREDICTS) study: Rationale, organization, design, and baseline characteristics.

Porter, Chad K / Riddle, Mark S / Gutierrez, Ramiro L / Princen, Fred / Strauss, Rick / Telesco, Shannon E / Torres, Joana / Choung, Rok Seon / Laird, Renee M / Leon, Francisco / Colombel, Jean-Frédéric / Murray, Joseph A

Contemporary clinical trials communications

2019 Volume 14, Page(s) 100345

Abstract: Purpose: The etiology of Inflammatory Bowel Disease (IBD) remains currently unknown but evidence would suggest that it results from a complex interplay between genetic susceptibility genes, the intestinal microbiome and the environment, resulting in an ... ...

Abstract	Purpose: The etiology of Inflammatory Bowel Disease (IBD) remains currently unknown but evidence would suggest that it results from a complex interplay between genetic susceptibility genes, the intestinal microbiome and the environment, resulting in an increased response towards microbial and self-antigens, followed by the development of pre-clinical intestinal inflammation as a precursor to overt clinical disease. Efforts are needed to provide insights into the characterization of the disease, the possible prediction of complications, and the detection of a pre-clinical disease state where, through early screening and intervention, disease course can be reversed, attenuated or even prevented. A consortium of academic, industry and governmental organization investigators initiated this study to enable an assessment of pre-disease biomarkers in patients newly diagnosed with Crohn's disease (CD) and ulcerative colitis (UC). Participants: A retrospective cohort of 1000 UC and 1000 CD cases with 500 matched controls was drawn from an active duty US military personnel population with relevant inclusion criteria with three associated pre-disease and a single disease-associated archived serum samples. Findings to date: The PREDICTS study has been established as a biorepository platform study to perform novel discovery and analysis efforts in the field of IBD and proteomic systems biology. Future plans: This study is poised to enable the assessment of novel biomarkers within the serum compartment to be analyzed with the goal of identifying pre-disease signals that ultimately predict disease risk, and further elucidate disease pathogenesis in the early stages of the disease process, and identify novel exposures that increase disease risk.
Language	English
Publishing date	2019-03-26
Publishing country	Netherlands
Document type	Journal Article
ISSN	2451-8654
ISSN (online)	2451-8654
DOI	10.1016/j.conctc.2019.100345
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Article ; Online: Serum Biomarkers Identify Patients Who Will Develop Inflammatory Bowel Diseases Up to 5 Years Before Diagnosis.

Torres, Joana / Petralia, Francesca / Sato, Takahiro / Wang, Pei / Telesco, Shannon E / Choung, Rok Seon / Strauss, Richard / Li, Xiao-Jun / Laird, Renee M / Gutierrez, Ramiro L / Porter, Chad K / Plevy, Scott / Princen, Fred / Murray, Joseph A / Riddle, Mark S / Colombel, Jean-Frederic

Gastroenterology

2020 Volume 159, Issue 1, Page(s) 96–104

Abstract: Background & aims: Biomarkers are needed to identify patients at risk for development of inflammatory bowel diseases. We aimed to identify serum biomarkers of Crohn's disease and ulcerative colitis that can be detected and quantified before diagnosis.!## ...

Abstract	Background & aims: Biomarkers are needed to identify patients at risk for development of inflammatory bowel diseases. We aimed to identify serum biomarkers of Crohn's disease and ulcerative colitis that can be detected and quantified before diagnosis. Methods: We obtained serum samples from patients archived before a diagnosis of Crohn's disease (n = 200) or ulcerative colitis (n = 199), as well as from 200 healthy individuals (controls), collected from 1998 through 2013 as part of the US Defense Medical Surveillance System. We measured levels of antibodies against microbes (anti-Saccharomyces cerevisiae IgA or IgG, anti-Escherichiacoli outer membrane porin C, anti-CBir1, anti-flagellin 2, anti-flagellin X, and perinuclear anti-neutrophil cytoplasmic antibodies) and 1129 proteins in each sample. We then used functional principal component analysis to derive the time-varying trajectory for each marker, which then was used in a multivariate model to predict disease status. Predictive performances at different prediagnosis timepoints were evaluated using area under the receiver operating characteristic curves (AUROCs). Biological pathways that were up-regulated in serum from patients with Crohn's disease were identified based on changes in protein abundance at different time periods preceding diagnosis. Results: We identified a panel of 51 protein biomarkers that were predictive of Crohn's disease within 5 years with an AUROC of 0.76 and a diagnosis within 1 year with an AUROC of 0.87. Based on the proteins included in the panel, imminent development of CD was associated with changes in the complement cascade, lysosomes, innate immune response, and glycosaminoglycan metabolism. Serum antibodies and proteins identified patients who received a diagnosis of ulcerative colitis within 5 years with an AUROC of only 0.56 and within 1 year with an AUROC of 0.72. Conclusions: We identified a panel of serum antibodies and proteins that were predictive of patients who will receive a diagnosis of Crohn's disease within 5 years with high accuracy. By contrast we did not identify biomarkers associated with future diagnosis of ulcerative colitis.
MeSH term(s)	Adult ; Antibodies, Antineutrophil Cytoplasmic/blood ; Antibodies, Antineutrophil Cytoplasmic/immunology ; Antibodies, Bacterial/blood ; Antibodies, Bacterial/immunology ; Antibodies, Fungal/blood ; Antibodies, Fungal/immunology ; Biomarkers/blood ; Case-Control Studies ; Colitis, Ulcerative/blood ; Colitis, Ulcerative/diagnosis ; Colitis, Ulcerative/immunology ; Crohn Disease/blood ; Crohn Disease/diagnosis ; Crohn Disease/immunology ; Escherichia coli/immunology ; Female ; Healthy Volunteers ; Humans ; Immunity, Innate ; Male ; Models, Statistical ; Predictive Value of Tests ; Prognosis ; Proteomics ; ROC Curve ; Saccharomyces cerevisiae/immunology ; Time Factors ; Young Adult
Chemical Substances	Antibodies, Antineutrophil Cytoplasmic ; Antibodies, Bacterial ; Antibodies, Fungal ; Biomarkers
Language	English
Publishing date	2020-03-09
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80112-4
ISSN	1528-0012 ; 0016-5085
ISSN (online)	1528-0012
ISSN	0016-5085
DOI	10.1053/j.gastro.2020.03.007
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Article ; Online: Analysis of Somatic Mutations in Cancer

Andrew J. Shih / Ravi Radhakrishnan / Shannon E. Telesco

Cancers, Vol 3, Iss 1, Pp 1195-

Molecular Mechanisms of Activation in the ErbB Family of Receptor Tyrosine Kinases

2011 Volume 1231

Abstract	The ErbB/EGFR/HER family of kinases consists of four homologous receptor tyrosine kinases which are important regulatory elements in many cellular processes, including cell proliferation, differentiation, and migration. Somatic mutations in, or over-expression of, the ErbB family is found in many cancers and is correlated with a poor prognosis; particularly, clinically identified mutations found in non-small-cell lung cancer (NSCLC) of ErbB1 have been shown to increase its basal kinase activity and patients carrying these mutations respond remarkably to the small tyrosine kinase inhibitor gefitinib. Here, we analyze the potential effects of the currently catalogued clinically identified mutations in the ErbB family kinase domains on the molecular mechanisms of kinase activation. Recently, we identified conserved networks of hydrophilic and hydrophobic interactions characteristic to the active and inactive conformation, respectively. Here, we show that the clinically identified mutants influence the kinase activity in distinctive fashion by affecting the characteristic interaction networks.
Keywords	ErbB/EGFR/HER kinase ; multiscale modeling ; somatic mutation ; ERK/Akt activation ; Neoplasms. Tumors. Oncology. Including cancer and carcinogens ; RC254-282 ; Internal medicine ; RC31-1245 ; Medicine ; R ; DOAJ:Oncology ; DOAJ:Medicine (General) ; DOAJ:Health Sciences
Subject code	616
Language	English
Publishing date	2011-03-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: A multiscale modeling approach to investigate molecular mechanisms of pseudokinase activation and drug resistance in the HER3/ErbB3 receptor tyrosine kinase signaling network.

Telesco, Shannon E / Shih, Andrew J / Jia, Fei / Radhakrishnan, Ravi

Molecular bioSystems

2011 Volume 7, Issue 6, Page(s) 2066–2080

Abstract: Multiscale modeling provides a powerful and quantitative platform for investigating the complexity inherent in intracellular signaling pathways and rationalizing the effects of molecular perturbations on downstream signaling events and ultimately, on the ...

Abstract	Multiscale modeling provides a powerful and quantitative platform for investigating the complexity inherent in intracellular signaling pathways and rationalizing the effects of molecular perturbations on downstream signaling events and ultimately, on the cell phenotype. Here we describe the application of a multiscale modeling scheme to the HER3/ErbB3 receptor tyrosine kinase (RTK) signaling network, which regulates critical cellular processes including proliferation, migration and differentiation. The HER3 kinase is a topic of current interest and investigation, as it has been implicated in mechanisms of resistance to tyrosine kinase inhibition (TKI) of EGFR and HER2 in the treatment of many human malignancies. Moreover, the commonly regarded status of HER3 as a catalytically inactive 'pseudokinase' has recently been challenged by our previous study, which demonstrated robust residual kinase activity for HER3. Through our multiscale model, we investigate the most significant molecular interactions that contribute to potential mechanisms of HER3 activity and the physiological relevance of this activity to mechanisms of drug resistance in an ErbB-driven tumor cell in silico. The results of our molecular-scale simulations support the characterization of HER3 as a weakly active kinase that, in contrast to its fully-active ErbB family members, depends upon a unique hydrophobic interface to coordinate the alignment of specific catalytic residues required for its activity. Translating our molecular simulation results of the uniquely active behavior of the HER3 kinase into a physiologically relevant environment, our HER3 signaling model demonstrates that even a weak level of HER3 activity may be sufficient to induce AKT signaling and TKI resistance in the context of an ErbB signaling-dependent tumor cell, and therefore therapeutic targeting of HER3 may represent a superior treatment strategy for specific ErbB-driven cancers.
MeSH term(s)	Amino Acid Sequence ; Antineoplastic Agents/pharmacology ; Computer Simulation ; Drug Resistance, Neoplasm ; Enzyme Activation ; Humans ; Hydrogen Bonding ; Hydrophobic and Hydrophilic Interactions ; Intracellular Signaling Peptides and Proteins/chemistry ; Lapatinib ; Models, Biological ; Molecular Dynamics Simulation ; Molecular Sequence Data ; Principal Component Analysis ; Protein Kinase Inhibitors/pharmacology ; Protein Kinase Inhibitors/therapeutic use ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Quinazolines/pharmacology ; Receptor, ErbB-3/chemistry ; Signal Transduction ; Structural Homology, Protein
Chemical Substances	Antineoplastic Agents ; Intracellular Signaling Peptides and Proteins ; Protein Kinase Inhibitors ; Quinazolines ; Lapatinib (0VUA21238F) ; Receptor, ErbB-3 (EC 2.7.10.1)
Language	English
Publishing date	2011-04-20
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2188635-0
ISSN	1742-2051 ; 1742-206X
ISSN (online)	1742-2051
ISSN	1742-206X
DOI	10.1039/c0mb00345j
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