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Digital kinases: A cell model for sensing, integrating and making choices
1Institut de Neurociències i Departament de Bioquímica i Biología Molecular; Unitat de Bioquímica; Facultad de Medicina; Universitat Autònoma de Barcelona; Barcelona, Spain.
Communicative & Integrative Biology
|June 30, 2010
Summary
Cellular stress sensors like JNK and AMPK exhibit ultrasensitive and digital responses. While JNK shows memory, AMPK does not, revealing distinct mechanisms for cell fate decisions.
Area of Science:
- Cellular signaling and signal transduction pathways.
- Biochemistry and molecular biology of protein kinases.
- Cellular decision-making processes in response to stress.
Background:
- Protein kinases are crucial for signal transduction and regulating cell fate.
- Key signaling properties for cellular sensors include ultrasensitivity, hysteresis, and digital responses.
- JNK (c-Jun N-terminal kinase) is a stress-activated protein kinase involved in cell death.
Purpose of the Study:
- To characterize Xenopus AMPK (AMP-activated protein kinase) signaling.
- To compare the signaling properties of AMPK and JNK in response to apoptotic stimuli.
- To investigate the role of ultrasensitivity, hysteresis, and digital responses in stress-induced cell fate decisions.
Main Methods:
- Utilized Xenopus oocytes for studying AMPK and JNK signaling.
- Applied hyperosmolar sorbitol as an apoptotic stimulus.
- Conducted single-cell analysis to determine kinase response characteristics.
Main Results:
- Xenopus AMPK is ultrasensitive to hyperosmolar sorbitol, similar to JNK.
- AMPK signaling does not exhibit hysteresis, unlike JNK.
- Both AMPK and JNK display digital (all-or-none) responses at the single-cell level.
- Graded responses are converted to digital during cytochrome c release.
Conclusions:
- Stress-activated protein kinases like AMPK and JNK possess distinct signaling properties (e.g., hysteresis) that influence cell fate.
- Cell death programs may involve the integration of multiple digital signals from stress sensors.
- The findings support a generalized model for cellular sensing, integration, and decision-making.
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