Related Experiment Videos
Molecular crosstalk between p70S6k and MAPK cell signaling pathways
Jason A Lehman1, Julian Gomez-Cambronero
1Department of Physiology and Biophysics, Wright State University School of Medicine, Dayton, OH 45435, USA.
Biochemical and Biophysical Research Communications
|June 11, 2002
Summary
The MEK inhibitor PD-98059 inactivated MAPK and p70S6K signaling. This study reveals molecular crosstalk between MAPK and p70S6K pathways, impacting neutrophil chemotaxis.
Area of Science:
- Cellular and Molecular Biology
- Immunology
- Signal Transduction
Background:
- Granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulates key signaling pathways.
- The Ras/MEK/MAPK and PI3-K/p70S6K pathways are critical in cellular functions.
- A molecular link between these pathways was previously suspected.
Purpose of the Study:
- To investigate the molecular crosstalk between the MAPK and p70S6K signaling pathways.
- To determine the role of this crosstalk in neutrophil chemotaxis.
Main Methods:
- Utilized the MEK inhibitor PD-98059 to assess pathway activity.
- Employed co-immunoprecipitation to examine protein interactions.
- Assessed enzymatic activity in immunoprecipitates.
- Investigated chemotaxis using specific inhibitors like rapamycin and PD-98059.
Main Results:
- PD-98059 inhibited GM-CSF-stimulated MAPK activity and partially inactivated p70S6K.
- MAPK and p70S6K proteins co-immunoprecipitated, indicating close proximity.
- Enzymatic activity of both kinases was detected in each other's immunoprecipitates.
- Both p70S6K (rapamycin) and MAPK (PD-98059) inhibitors impaired neutrophil chemotaxis.
Conclusions:
- Established a molecular connection between the MAPK and p70S6K signaling pathways.
- Demonstrated that this kinase crosstalk is essential for neutrophil chemotaxis.
- Highlighted the significance of these pathways in the function of mature phagocytes.