Works (7)

Updated: July 5th, 2023 15:50

2014 journal article

Data-driven modeling reconciles kinetics of ERK phosphorylation, localization, and activity states


By: S. Ahmed n, K. Grant n, L. Edwards n, A. Rahman n, M. Cirit n, M. Goshe n, J. Haugh n

author keywords: growth factor receptors; mitogen-activated protein kinases; negative feedback; nucleocytoplasmic shuttling; mathematical model
MeSH headings : Active Transport, Cell Nucleus; Animals; Extracellular Signal-Regulated MAP Kinases / chemistry; Extracellular Signal-Regulated MAP Kinases / metabolism; Feedback, Physiological; Kinetics; Mice; Models, Theoretical; NIH 3T3 Cells; Phosphorylation; Protein Transport / genetics; Receptors, Growth Factor / genetics; Signal Transduction / genetics
Sources: Web Of Science, ORCID
Added: August 6, 2018

2012 journal article

Data-driven modelling of receptor tyrosine kinase signalling networks quantifies receptor-specific potencies of PI3K-and Ras-dependent ERK activation


By: M. Cirit n & J. Haugh n

author keywords: computational biology; cross-talk; growth factor; kinetic analysis; mitogen-activated protein kinase (MAPK); receptor tyrosine kinase
MeSH headings : Animals; Becaplermin; Computer Simulation; Extracellular Signal-Regulated MAP Kinases / genetics; Extracellular Signal-Regulated MAP Kinases / metabolism; Fibroblast Growth Factor 2 / genetics; Fibroblast Growth Factor 2 / metabolism; Fibroblasts / metabolism; Gene Expression Regulation, Enzymologic; Humans; Kinetics; Mice; Models, Biological; NIH 3T3 Cells; Phosphatidylinositol 3-Kinases / genetics; Phosphatidylinositol 3-Kinases / metabolism; Proto-Oncogene Proteins c-sis / genetics; Proto-Oncogene Proteins c-sis / metabolism; Receptor Protein-Tyrosine Kinases / genetics; Receptor Protein-Tyrosine Kinases / metabolism; Receptors, Fibroblast Growth Factor / genetics; Receptors, Fibroblast Growth Factor / metabolism; Signal Transduction
TL;DR: It is shown that, whereas the FGF stimulation of PI3K signalling is relatively weak, this deficiency is compensated for by a more potent Ras-dependent activation of ERK, and the ERK pathway is activated to a greater extent in cells co-stimulated with FGF and PDGF, relative to the saturated levels achieved with either ligand alone. (via Semantic Scholar)
Sources: Web Of Science, ORCID
Added: August 6, 2018

2012 journal article

Systemic Perturbation of the ERK Signaling Pathway by the Proteasome Inhibitor, MG132

PLOS ONE, 7(11).

By: M. Cirit n, K. Grant n & J. Haugh n

Ed(s): L. Buday

MeSH headings : Animals; Computer Simulation; Dual-Specificity Phosphatases / metabolism; Embryo, Mammalian / cytology; Enzyme Activation / drug effects; Fibroblast Growth Factors / pharmacology; Fibroblasts / cytology; Fibroblasts / drug effects; Fibroblasts / enzymology; Humans; Leupeptins / pharmacology; MAP Kinase Signaling System / drug effects; Mesoderm / cytology; Mice; Mitogen-Activated Protein Kinase Kinases / metabolism; NIH 3T3 Cells; Phosphorylation / drug effects; Platelet-Derived Growth Factor / pharmacology; Proteasome Inhibitors / pharmacology; Up-Regulation / drug effects
TL;DR: It is shown that the effects of MG132 treatment on ERK signaling are more widespread, leading to a reduction in activation of the upstream kinase MEK, suggesting that MG132 systemically perturbs the intracellular phosphoproteome, impactingERK signaling by reducing phosphorylation status at multiple levels of the kinase cascade. (via Semantic Scholar)
Sources: Web Of Science, ORCID
Added: August 6, 2018

2011 journal article

Allosteric Modulation of Ras-GTP Is Linked to Signal Transduction through RAF Kinase


By: G. Buhrman*, V. Kumar, M. Cirit n, J. Haugh n & C. Mattos*

MeSH headings : Allosteric Regulation; Allosteric Site; Animals; Guanosine Triphosphate / metabolism; Kinetics; Mice; Mutation, Missense; NIH 3T3 Cells; Protein Conformation; Protein Stability; Signal Transduction; raf Kinases / metabolism; ras Proteins / genetics; ras Proteins / metabolism
TL;DR: The allosteric switch is linked to the control of signaling in the Ras/Raf/MEK/ERK pathway, supporting a GTPase-activating protein-independent model for duration of the Ras-Raf complex. (via Semantic Scholar)
Sources: Web Of Science, ORCID
Added: August 6, 2018

2011 article

PI3K-dependent cross-talk interactions converge with Ras as quantifiable inputs integrated by Erk (vol 5, pg 246, 2009)

Wang, C.-C., Cirit, M., & Haugh, J. M. (2011, August). MOLECULAR SYSTEMS BIOLOGY, Vol. 7.

By: C. Wang n, M. Cirit n & J. Haugh n

TL;DR: The effects of expressing wild-type and genuine G12V H-Ras in the authors' cells, using the samemethods as in the published article, are presented. (via Semantic Scholar)
Sources: Web Of Science, ORCID
Added: August 6, 2018

2010 journal article

Stochastic Model of Integrin-Mediated Signaling and Adhesion Dynamics at the Leading Edges of Migrating Cells


By: M. Cirit n, M. Krajcovic n, C. Choi*, E. Welf n, A. Horwitz* & J. Haugh n

Ed(s): A. Asthagiri

MeSH headings : Animals; CHO Cells; Cell Adhesion / physiology; Cell Movement / physiology; Cell Surface Extensions / metabolism; Computational Biology / methods; Computer Simulation; Cricetinae; Cricetulus; Extracellular Matrix / metabolism; Green Fluorescent Proteins / genetics; Green Fluorescent Proteins / metabolism; Integrins / metabolism; Models, Biological; Myosins / metabolism; Paxillin / genetics; Paxillin / metabolism; Signal Transduction / physiology; Stochastic Processes; rac GTP-Binding Proteins / metabolism
TL;DR: This work has formulated a quantitative model of leading edge dynamics combining mechanistic and phenomenological elements and studied its features through classical bifurcation analysis and stochastic simulation, showing that the qualitative behavior of the model is most sensitive to parameters characterizing the influence of stable adhesion and myosin. (via Semantic Scholar)
UN Sustainable Development Goal Categories
10. Reduced Inequalities (OpenAlex)
Sources: Web Of Science, ORCID
Added: August 6, 2018

2010 journal article

Systematic Quantification of Negative Feedback Mechanisms in the Extracellular Signal-regulated Kinase (ERK) Signaling Network


By: M. Cirit n, C. Wang n & J. Haugh n

MeSH headings : Animals; Extracellular Signal-Regulated MAP Kinases / metabolism; Feedback, Physiological; Humans; Immunoblotting; Kinetics; Mice; Mitogen-Activated Protein Kinases / metabolism; NIH 3T3 Cells; Phosphorylation; Signal Transduction; ras Proteins / metabolism
TL;DR: This work takes a systematic approach to parse the magnitudes of multiple regulatory mechanisms that attenuate ERK activation through canonical (Ras- dependent) and non-canonical (PI3K-dependent) pathways and demonstrates that kinetic models of signaling networks, trained on a sufficient diversity of quantitative data, can be reasonably comprehensive, accurate, and predictive in the dynamical sense. (via Semantic Scholar)
Sources: Web Of Science, ORCID
Added: August 6, 2018

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