SH2 Domains Serve as Lipid-Binding Modules for pTyr-Signaling Proteins

Cited 30 time in webofscience Cited 0 time in scopus
  • Hit : 33
  • Download : 0
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.
Publisher
CELL PRESS
Issue Date
2016-04
Language
English
Article Type
Article
Keywords

TYROSINE KINASE; PLASMA-MEMBRANE; SCAFFOLD PROTEINS; LIVING CELLS; PHOSPHOINOSITIDE; ORGANIZATION; SPECIFICITY; RESIDUES; DYNAMICS; ELECTROSTATICS

Citation

MOLECULAR CELL, v.62, no.1, pp.7 - 20

ISSN
1097-2765
DOI
10.1016/j.molcel.2016.01.027
URI
http://hdl.handle.net/10203/240764
Appears in Collection
MSE-Journal Papers(저널논문)
Files in This Item
There are no files associated with this item.
This item is cited by other documents in WoS
⊙ Detail Information in WoSⓡ Click to see webofscience_button
⊙ Cited 30 items in WoS Click to see citing articles in records_button

qr_code

  • mendeley

    citeulike


rss_1.0 rss_2.0 atom_1.0