Binding of pleckstrin homology domains to WD40/beta-transducin repeat containing segments of the protein product of the Lis-1 gene.

In previous experiments we demonstrated an interaction between certain pleckstrin homology (PH) domains and regions containing the so-called WD40 (or beta-transducin) repeats of the beta subunit of trimeric G-proteins (G beta), a finding we here extend to the PH domains of the src-related tyrosine kinase TecIIa and the GTPase dynamin. To examine the possibility that WD40 repeats in molecules other than G beta might also bind PH domains we examined PAFAH-45, the protein product of the Lis-1 gene, which contains 7 WD40 repeats. We found that 1) Purified PAFAH-45 binds PH domain constructs in vitro. 2) Protein constructs expressing all 7 WD40 repeats of PAFAH-45 but lacking the N-terminal non WD40 region also bind PH domains of beta-adrenergic receptor kinase, beta-spectrin, TecIIa and dynamin but with a differing hierarchy of affinities than that seen with G beta. 3). PAFAH-45 WD40 repeats will reduce the binding of PH domains to brain G beta and brain G beta gamma will reduce the binding of PH domains to PAFAH-45. These data support the hypothesis that PH domain/WD40 interactions are involved in a wide variety of important protein/protein interactions.