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Amide Hydrogen/Deuterium Exchange & MALDI-TOF Mass Spectrometry Analysis of Pak2 Activation
Published on: November 26, 2011
Functional interaction between c-Abl and the p21-activated protein kinase gamma-PAK
J Roig1, P T Tuazon, P A Zipfel
1Department of Biochemistry, University of California, Riverside, CA 92521, USA.
Summary
Gamma-PAK protein kinase activates c-Abl tyrosine kinase activity. In turn, c-Abl phosphorylates and down-regulates gamma-PAK, forming a negative feedback loop.
Area of Science:
- Molecular Biology
- Cell Signaling
- Protein Kinase Interactions
Background:
- Gamma-PAK (p21-activated protein kinase) is a stress-activated kinase with cytostatic properties.
- Nonreceptor protein tyrosine kinase c-Abl plays roles in cellular processes.
- The interaction and regulation between gamma-PAK and c-Abl are not well understood.
Purpose of the Study:
- To investigate the functional interaction between gamma-PAK and c-Abl.
- To elucidate the regulatory mechanisms governing their activities.
Main Methods:
- In vivo association studies.
- In vitro kinase assays.
- Cell-based assays involving cotransfection (HEK 293T cells).
- Ubiquitination and proteasome inhibition studies.
Main Results:
- Gamma-PAK associates with c-Abl in vivo.
- Gamma-PAK phosphorylates and activates c-Abl.
- C-Abl phosphorylates gamma-PAK on tyrosine residues, leading to its down-regulation and inactivation.
- Gamma-PAK activity is regulated by ubiquitination and proteasomal degradation.
Conclusions:
- A functional crosstalk exists between gamma-PAK and c-Abl.
- Gamma-PAK stimulates c-Abl activity, while c-Abl negatively regulates gamma-PAK activity.
- This interaction suggests a negative feedback loop controlling cellular signaling pathways.
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