Related Experiment Video

Updated: Jun 1, 2026

Spatial and Temporal Analysis of Active ERK in the C. elegans Germline
08:40

Spatial and Temporal Analysis of Active ERK in the C. elegans Germline

Published on: November 29, 2016

Lose and gain: impacts of ERK5 and JNK cascades on each other

Sundaramurthy Pandurangan, Sunita Gakkhar

    Systems and Synthetic Biology
    |June 2, 2011
    PubMed
    Abstract

    Insights

    Mathematical models reveal that cross-talks and feedback loops in Extracellular signal-regulated kinases 5 (ERK5) and c-Jun N-terminal kinases (JNK) pathways can cause transient ERK5 activation without external signals.

    Area of Science:

    • Biochemistry
    • Cell Signaling
    • Systems Biology

    Background:

    • Kinase cascades, including ERK5 and JNK pathways, are crucial for cellular responses to stimuli.
    • Interactions between signaling pathways (cross-talks) and feedback loops can significantly modify pathway behavior.
    • Understanding these complex regulatory mechanisms is essential for deciphering diverse biological outcomes.

    Purpose of the Study:

    • To mathematically model and analyze the impact of cross-talks and feedback loops on ERK5 and JNK signaling pathways.
    • To predict how these regulatory elements influence pathway activation dynamics.
    • To investigate the conditions leading to aberrant pathway activation.

    Main Methods:

    • Development of mathematical models based on enzyme kinetic reactions.
    • Simulation and analysis of ERK5 and JNK cascade models incorporating cross-talks and feedback loops.
    • Evaluation of pathway responses under various signaling conditions.

    Main Results:

    • Cross-talks between ERK5 and JNK pathways showed no significant impact on their individual activation levels.
    • The combined presence of cross-talks and feedback loops in the ERK5 and JNK cascades led to transient ERK5 activation, even without input signals.
    • The study identified specific conditions under which these pathways exhibit unusual activation patterns.

    Conclusions:

    • Cross-talks alone between ERK5 and JNK pathways do not substantially alter their activation.
    • Feedback loops, in conjunction with cross-talks, play a critical role in modulating ERK5 and JNK pathway dynamics, potentially causing signal-independent activation.
    • Experimental validation and parameter determination are planned to confirm these modeling-based findings.
    Keywords:
    Cross-talksDynamic systemsERK5 cascadeEnzyme kinetic reactionsFeedback loopsJNK cascade

    More Related Videos

    Assaying Protein Kinase Activity with Radiolabeled ATP08:05

    Assaying Protein Kinase Activity with Radiolabeled ATP

    Published on: May 26, 2017

    Light-mediated Reversible Modulation of the Mitogen-activated Protein Kinase Pathway during Cell Differentiation and Xenopus Embryonic Development09:32

    Light-mediated Reversible Modulation of the Mitogen-activated Protein Kinase Pathway during Cell Differentiation and Xenopus Embryonic Development

    Published on: June 15, 2017

    Related Concept Videos

    MAPK Signaling Cascades01:07

    MAPK Signaling Cascades

    Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
    Amplifying Signals via Enzymatic Cascade01:22

    Amplifying Signals via Enzymatic Cascade

    When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze the...
    Interactions Between Signaling Pathways01:19

    Interactions Between Signaling Pathways

    Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
    Convergence and divergence, and cross-talk between signaling pathways
    Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
    Intracellular Signaling Cascades01:24

    Intracellular Signaling Cascades

    Once a ligand binds to a receptor, the signal is transmitted through the membrane and into the cytoplasm. The continuation of a signal in this manner is called signal transduction. Signal transduction only occurs with cell-surface receptors, which cannot interact with most components of the cell, such as DNA. Only internal receptors can interact directly with DNA in the nucleus to initiate protein synthesis. When a ligand binds to its receptor, conformational changes occur that affect the...
    Intracellular Signaling Cascades01:24

    Intracellular Signaling Cascades

    Once a ligand binds to a receptor, the signal is transmitted through the membrane and into the cytoplasm. The continuation of a signal in this manner is called signal transduction. Signal transduction only occurs with cell-surface receptors, which cannot interact with most components of the cell, such as DNA. Only internal receptors can interact directly with DNA in the nucleus to initiate protein synthesis. When a ligand binds to its receptor, conformational changes occur that affect the...
    cAMP-dependent Protein Kinase Pathways01:25

    cAMP-dependent Protein Kinase Pathways

    Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...