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Cited 7 time in webofscience Cited 7 time in scopus
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Lipids Regulate Lck Protein Activity through Their Interactions with the Lck Src Homology 2 Domain.

Title
Lipids Regulate Lck Protein Activity through Their Interactions with the Lck Src Homology 2 Domain.
Authors
Sheng, RJung, DJSilkov, AKim, HSingaram, IWang, ZGXin, YKim, EPark, MJThiagarajan-Rosenkranz, PSmrt, SHonig, BBaek, KRyu, SLorieau, JKim, YMCho, W
Date Issued
Aug-2016
Publisher
American Society for Biochemistry and Molecular Biology Inc.
Abstract
Lymphocyte-specific protein-tyrosine kinase (Lck) plays an essential role in T cell receptor (TCR) signaling and T cell development, but its activation mechanism is not fully understood. To explore the possibility that plasma membrane (PM) lipids control TCR signaling activities of Lck, we measured the membrane binding properties of its regulatory Src homology 2 (SH2) and Src homology 3 domains. The Lck SH2 domain binds anionic PM lipids with high affinity but with low specificity. Electrostatic potential calculation, NMR analysis, and mutational studies identified the lipid-binding site of the Lck SH2 domain that includes surface-exposed basic, aromatic, and hydrophobic residues but not the phospho-Tyr binding pocket. Mutation of lipid binding residues greatly reduced the interaction of Lck with the chain in the activated TCR signaling complex and its overall TCR signaling activities. These results suggest that PM lipids, including phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol 3,4,5-trisphosphate, modulate interaction of Lck with its binding partners in the TCR signaling complex and its TCR signaling activities in a spatiotemporally specific manner via its SH2 domain.
URI
http://oasis.postech.ac.kr/handle/2014.oak/37107
ISSN
0021-9258
Article Type
Article
Citation
Journal of Biological Chemistry, vol. 291, no. 34, page. 17639 - 17650, 2016-08
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 RYU, SUNG HO
Dept of Life Sciences
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