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Pleckstrin homology domains and the cytoskeleton
Author(s) -
Lemmon Mark A.,
Ferguson Kathryn M.,
Abrams Charles S.
Publication year - 2002
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(01)03243-4
Subject(s) - pleckstrin homology domain , guanine nucleotide exchange factor , spectrin , cytoskeleton , phosphatidylinositol , phosphotyrosine binding domain , microbiology and biotechnology , biology , biochemistry , binding site , actin , membrane , kinase , signal transduction , proto oncogene tyrosine protein kinase src , cell , sh2 domain
Pleckstrin homology (PH) domains are 100–120 amino acid protein modules best known for their ability to bind phosphoinositides. All possess an identical core β‐sandwich fold and display marked electrostatic sidedness. The binding site for phosphoinositides lies in the center of the positively charged face. In some cases this binding site is well defined, allowing highly specific and strong ligand binding. In several of these cases the PH domains specifically recognize 3‐phosphorylated phosphoinositides, allowing them to drive membrane recruitment in response to phosphatidylinositol 3‐kinase activation. Examples of these PH domain‐containing proteins include certain Dbl family guanine nucleotide exchange factors, protein kinase B, PhdA, and pleckstrin‐2. PH domain‐mediated membrane recruitment of these proteins contributes to regulated actin assembly and cell polarization. Many other PH domain‐containing cytoskeletal proteins, such as spectrin, have PH domains that bind weakly, and to all phosphoinositides. In these cases, the individual phosphoinositide interactions may not be sufficient for membrane association, but appear to require self‐assembly of their host protein and/or cooperation with other anchoring motifs within the same molecule to drive membrane attachment.