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Imaging Spatial Reorganization of a MAPK Signaling Pathway Using the Tobacco Transient Expression System

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Coordination of crosstalk between MAPK-PKC pathways: an exploratory study.

S N Sreenath¹, R Soebiyanto, M D Mesarovic

¹Systems Biology Initiative and Electrical Engineering and Computer Science Department, Case Western Reserve University, Cleveland, OH 44106, USA. n.sreenath@case.edu

IET Systems Biology

|March 21, 2007

Summary

Cell adaptation involves interconnected signaling pathways like mitogen-activated protein kinase (MAPK) and protein kinase C (PKC). The Phospholipase A2 (PLA2) subsystem acts as a coordinator, enabling pathway activation and self-activation without external input.

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Area of Science:

Cellular biology
Systems biology
Biochemistry

Background:

Cellular responses to stimuli rely on complex signaling networks.
Interactions between pathways like MAPK and PKC are crucial for cellular adaptation.
Understanding adaptive mechanisms requires analyzing pathway coordination.

Purpose of the Study:

To investigate cell adaptation as an organizing principle between MAPK and PKC pathways.
To identify pathway components responsible for adaptive behavior and coordination.
To explore the role of a coordinator in regulating pathway activity.

Main Methods:

Utilized a multilevel system representation of interconnected signaling pathways.
Employed a modularized MAPK-PKC mathematical model for in silico experiments.
Conducted guided parametric simulations to identify the coordinator subsystem.

Main Results:

The Phospholipase A2 (PLA2) subsystem was identified as the key coordinator.
Varying PLA2 parameters activated dormant pathways and initiated self-activation.
Demonstrated the system's ability to activate without external stimuli, showing bounded autonomy.

Conclusions:

The PLA2 subsystem plays a critical role in coordinating MAPK and PKC signaling for cell adaptation.
The principle of bounded autonomy is relevant in cellular signaling networks.
Parameter modulation of the coordinator is essential for adaptive pathway regulation.