SH2 domains serve as lipid binding modules for pTyr-signaling proteins
SCIE
SCOPUS
- Title
- SH2 domains serve as lipid binding modules for pTyr-signaling proteins
- Authors
- Park, MJ; Sheng, R; Silkov, A; Jung, DJ; Wang, ZG; Xin, Y; Kim, H; Thiagarajan-Rosenkranz, P; Song, S; Yoon, Y; Nam, W; Kim, I; Kim, E; Lee, DG; Chen, Y; Singaram, I; Wang, L; Jang, MH; Hwang, CS; Honig, B; Ryu, S; Lorieau, J; Kim, YM; Cho, W
- Date Issued
- 2016-04-07
- Publisher
- Cell Press
- Abstract
- The Src-homology 2 (SH2) domain is a protein interaction domain that directs myriad phosphotyrosine (pY)-signaling pathways. Genome-wide screening of human SH2 domains reveals that similar to 90% of SH2 domains bind plasma membrane lipids and many have high phosphoinositide specificity. They bind lipids using surface cationic patches separate from pY-binding pockets, thus binding lipids and the pY motif independently. The patches form grooves for specific lipid headgroup recognition or flat surfaces for non-specific membrane binding and both types of interaction are important for cellular function and regulation of SH2 domain-containing proteins. Cellular studies with ZAP70 showed that multiple lipids bind its C-terminal SH2 domain in a spatiotemporally specific manner and thereby exert exquisite spatiotemporal control over its protein binding and signaling activities in T cells. Collectively, this study reveals how lipids control SH2 domain-mediated cellular protein-protein interaction networks and suggest a new strategy for therapeutic modulation of pY-signaling pathways.
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/36031
- DOI
- 10.1016/J.MOLCEL.2016.01.027
- ISSN
- 1097-2765
- Article Type
- Article
- Citation
- Molecular Cell, vol. 62, no. 1, page. 7 - 20, 2016-04-07
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