Related Experiment Videos
Stimulation by phospholipids of a protein-tyrosine-phosphatase containing two src homology 2 domains
Z Zhao1, S H Shen, E H Fischer
1Department of Biochemistry, University of Washington, Seattle 98195.
Abstract:
PTP1C, a protein-tyrosine-phosphatase (protein-tyrosine-phosphate phosphohydrolase, EC 3.1.3.48) containing two src homology 2 domains, is poorly active when assayed with various protein substrates in vitro. Its activity is stimulated > 1000-fold by anionic phospholipids when myelin basic protein or mitogen-activated protein kinase is used as substrate but reduced in the presence of several other substrates. Data are presented to indicate a direct interaction of the enzyme with phospholipids. Enzyme stimulation directed only toward certain specific substrates is interpreted by assuming that these compounds also bind to the phospholipid vesicles where they will be subjected to rapid enzymatic attack. A possible regulation of PTP1C by its translocation to the cell membrane is hypothesized.
Insights
Anionic phospholipids significantly enhance the activity of protein-tyrosine-phosphatase 1C (PTP1C) towards specific substrates. This suggests a regulatory mechanism involving phospholipid interactions and potential translocation to the cell membrane.
Area of Science:
- Biochemistry
- Molecular Biology
- Enzymology
Background:
- Protein-tyrosine-phosphatase 1C (PTP1C) possesses two src homology 2 domains.
- PTP1C exhibits low basal activity with many protein substrates in vitro.
Purpose of the Study:
- To investigate the regulatory mechanisms of PTP1C activity.
- To explore the role of phospholipids in PTP1C enzymatic function.
Main Methods:
- Enzyme assays using various protein substrates.
- Investigating the effect of anionic phospholipids on PTP1C activity.
- Analyzing enzyme-substrate interactions with phospholipids.
Main Results:
- Anionic phospholipids stimulated PTP1C activity over 1000-fold with myelin basic protein and mitogen-activated protein kinase.
- Phospholipid stimulation was substrate-specific, with reduced activity for other substrates.
- Direct interaction between PTP1C and phospholipids was demonstrated.
Conclusions:
- PTP1C activity is significantly modulated by anionic phospholipids.
- Substrate-specific stimulation suggests a model where substrates bind to phospholipid vesicles for enhanced enzymatic attack.
- Translocation of PTP1C to the cell membrane is a potential regulatory mechanism.