A diverse array of molecules involved in signal transduction have recently been recognised as containing a new homology domain, the pleckstrin homology (PH) domain. These include kinases (both serine/threonine and tyrosine specific), all currently known mammalian phospholipase Cs, GTPases, GTPase-activating proteins, GTPase-exchange factors, "adapter" proteins, cytoskeletal proteins, and kinase substrates. This has sparked a new surge of research into elucidating its structure and function. The NMR solution structure of the PH domains of beta-spectrin and pleckstrin (the N-terminal domain) both display a core consisting of seven anti-parallel beta-sheet strands. The carboxy terminus is folded into a long alpha-helix. The molecule is electrostatically polarised and contains a pocket which may be involved in the binding of a ligand. The PH domains overall topological relatedness to the retinoid binding protein family of molecules would suggest a lipid ligand could bind to this pocket. The prime function of the PH domain still remains to be elucidated. However, it has been shown to be important in signal transduction, most probably by mediating protein-protein interactions. An extended PH domain of the beta-adrenergic receptor kinase (beta ARK), as well as that of several other molecules, can bind to beta gamma subunits of the heterotrimeric G-proteins. The possibility that the PH domain, which is found in so many signalling molecules, being generally involved in beta gamma binding is provocative of implicating these proteins in G-protein signal transduction.(ABSTRACT TRUNCATED AT 250 WORDS)