Display Settings:

Format

Send to:

Choose Destination
We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Mol Endocrinol. 2002 Jan;16(1):85-99.

AR and ER interaction with a p21-activated kinase (PAK6).

Author information

  • 1Cancer Biology Program, Hematology-Oncology Division, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA.

Abstract

A human protein termed p21-activated kinase 6 (PAK6), based on homology to the PAK family of serine/threonine kinases, was cloned as an AR interacting protein. PAK6 was a 75-kDa protein with a predicted N-terminal Cdc42/Rac interactive binding domain and a C-terminal kinase domain. PAK6 bound strongly to GTP-Cdc42 and weakly to GTP-Rac. In contrast to most PAKs, kinase activity was not stimulated by Cdc42 or Rac, but could be stimulated by AR binding. PAK6 interacted with the intact AR in a mammalian one-hybrid assay and bound in vitro, without ligand, to the hinge region between the AR DNA- and ligand-binding domains. PAK6 also bound to the ERalpha, and binding was enhanced by 4-hydroxytamoxifen. AR and ERalpha transcriptional activities were inhibited by PAK6 in transient transfections with episomal and integrated reporter genes. AR inhibition was not reversed by transfection with an activated Cdc42 mutant, Cdc42V12, which by itself also inhibited AR transactivation. Epitope-tagged PAK6 was primarily cytoplasmic in the absence or presence of AR and hormone. PAK6 transcripts were expressed most highly in brain and testis, with lower levels in multiple tissues including prostate and breast. PAK6 interaction provides a mechanism for cross-talk between steroid hormone receptors and Cdc42-mediated signal transduction pathways and could contribute to the effects of tamoxifen in breast cancer and in other tissues.

PMID:
11773441
[PubMed - indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Atypon
    Loading ...
    Write to the Help Desk