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PTEN binding properties for different model membrane morphologies
Author(s) -
Gericke Arne,
Ross Alonzo H,
King Katrice E.,
Neuman Brittany M.,
Jiang Zhiping
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.993.6
Subject(s) - pten , vesicle , chemistry , biophysics , bilayer , receptor–ligand kinetics , lipid bilayer , kinetics , fluorescence microscope , membrane , fluorescence anisotropy , fluorescence , biochemistry , biology , signal transduction , receptor , pi3k/akt/mtor pathway , quantum mechanics , physics
PTEN acts as an agonist to PI 3‐kinase signaling by removing the phosphate group in the 3 position of PI(3,4,5)P3. PTEN membrane association and activation requires the interaction with PI(4,5)P2 and PS. In biological membranes, these lipids may form upon interaction with other molecular entities domains that exhibit distinct compositional and physicochemical characteristics. It is the objective of this study to elucidate the relationship between lipid bilayer morphologies and the extent of PTEN binding and PTEN membrane association dynamics. Methods To characterize lipid morphologies in the absence and presence of PTEN, we used fluorescence microscopy measurements of mixed lipid giant unilamellar vesicles (GUVs). PTEN binding extent is evaluated using SPR and Trp fluorescence measurements. The binding kinetics of PTEN bilayer interaction is elucidated using stopped‐flow experiments. Results The interaction of PTEN with mixed PC/PI(4,5)P2 model membranes results in the formation of PI(4,5)P2 enriched domains. Domain formation in the absence of PTEN is also observed when cholesterol is added when making mixed PC/PI(4,5)P2 vesicles. We find an increased PTEN binding in the presence of PI(4,5)P2 domains, which is probably due to increased local PI(4,5)P2 concentration. This work was supported by NIH R01 NS021716 and NSF CHEM 0922848 and 1058719.