Androgen receptor specifically interacts with a novel p21-activated kinase, PAK6

The androgen receptor (AR) is a hormone-dependent transcription factor that plays important roles in male sexual differentiation and development. Tran scription activation by steroid hormone receptors, such as the androgen rec eptor, is mediated through interaction with cofactors. We recently identifi ed a novel AR-interacting protein, provisionally termed PAK6, that shares a high degree of sequence similarity with p21-activated kinases (PAKs). PAK6 is a 75-kDa protein that contains a putative amino-terminal Cdc42/Rac inte ractive binding motif and a carboxyl-terminal kinase domain. A domain-speci fic and ligand dependent interaction between AR and PAK6 was further confir med in vivo and in vitro. Northern blot analysis revealed that PAK6 is high ly expressed in testis and prostate tissues. Most importantly, immunofluore scence studies showed that PAK6 cotranslocates into the nucleus with AR in response to androgen, Transient transfection experiments showed that PAK6 s pecifically repressed AR-mediated transcription, This report identifies a n ovel function for a PAK-homologous protein and suggests a potential unique mechanism by which other signal transduction pathways may cross-talk with A R pathways to regulate AR function in normal and malignant prostate cells.