PHドメイン　新しい機能性ドメインとしての可能性

抄録

A pleckstrin homology (PH) domain is an approximately 100 amino acid region of sequence homology present in numerous proteins involved in signal transduction and growth control. The three dimensional structures of several PH domains demonstrate that they consist of a β-barrel of seven antiparallel β-sheets and a carboxyl-terminal amphiphilic α-helix. Several ligands capable of binding to PH domains have been identified including phosphatidylinositol 4, 5bisphosphate and the βγ subunits of heterotrimeric G proteins, which bind to the amino and carboxyl-termini of the PH domain, respectively. Furthermore, several isoforms of protein kinase C appear to bind to some PH domains. A general function of PH domains may be to anchor PH domain-containing proteins to the appropriate membrane-compartment. The membrane localization of PH domain-containing proteins may require cooperative multiple ligand binding to the PH domain. Finally, the heterogeneity of sequences among various PH domains may prove to be the basis for differences in the regulation and specificity of PH domain-ligand interaction in a fashion similar to SH2 and SH3 domains. The function of the PH domain and the mechanisms of PH domain action seem to be quite complex.