The PH domain: a common piece in the structural patchwork of signalling proteins

Abstract

The 'pleckstrin homology' domain is an approximately 100-residue protein module that has recently been added to the domain catalogue of signalling proteins. For this review we have made an extensive database search using a profile search method, and found a number of additional proteins that may contain PH domains. The PH domain is present in many kinases, isoforms of phospholipase C, GTPases, GTPase-activating proteins and nucleotide-exchange factors, including such proteins as Vav, Dbl and Bcr, and there are two PH domains in a guanine-nucleotide releasing factor of Ras. Many PH-domain-containing proteins interact with GTP-binding proteins. We have also identified a PH domain in beta-adrenergic receptor kinase exactly in the region that has already been shown to be involved in binding to the beta and gamma subunits of a heterotrimeric G protein. This suggests that PH domains may be involved in interactions with GTP-binding proteins.