IDENTIFICATION OF NOVEL PLECKSTRIN HOMOLOGY (PH) DOMAINS PROVIDES A HYPOTHESIS FOR PH DOMAIN FUNCTION

Pleckstrin homology (PH) domains are difficulat to find in protein sequence databases with widely used computer programs. A simple program developed to overcome this difficulty identified three proteins containing previously unrecognized PH domains; the β-adrenergic receptor kinase (β-ARK), the tecA protein kinase and the insulin receptor substrate protein IRS-1. The region of β-ARK cotaining the novel PH domain coincides with that previously shown to bind the βγ subunits of trimeric G-proteins, suggesting a general hypothesis for PH domain function. PH domains were then found at the N-termini of the tecA homologues Btk and itk. In line with the hypothesis a point mutation in the PH domain of Btk is associated with defects in signal transduction. © 1993 Academic Press, Inc.