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Differential effects of lipids on cellular activities of SH2 domain‐containing Proteins
Author(s) -
Singaram Indira,
Cho Wonhwa
Publication year - 2017
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.31.1_supplement.946.6
Subject(s) - sh2 domain , proto oncogene tyrosine protein kinase src , microbiology and biotechnology , biochemistry , chemistry , phosphotyrosine binding domain , mutant , protein–protein interaction , plasma protein binding , tyrosine , sh3 domain , phosphorylation , biology , gene
SH2 (Src Homology 2) domain is a prototypical protein interaction domain that specifically recognizes a phosphorylated tyrosine (pY) motif. Our recent study showed that a large majority of human SH2 domains bind lipids in the plasma membrane (PM) with high affinity using an alternate cationic patch (ACP) that is topologically distinct from the cationic pY‐binding pocket. However, some SH2 domains lacking ACP bind PM lipids, including phosphoinositides, in their pY‐binding pockets. To understand the differential effects of lipids on ACPs and pY pockets of SH2 domains on the cellular activities of their host proteins, we performed computational, biophysical and cellular activity and imaging analyses with various SH2 domain‐containing proteins and their lipid‐binding site mutants. Our results demonstrate highly variable mechanisms by which lipids cellular protein‐protein interactions and modulate signaling activities of these proteins in immune cells. Support or Funding Information NIH GM68849