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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. Transcription activation by steroid hormone receptors, such as the androgen receptor, is mediated through interaction with cofactors. We recently identified 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 interactive binding motif and a carboxyl-terminal kinase domain. A domain-specific and ligand-dependent interaction between AR and PAK6 was further confirmed in vivo and in vitro. Northern blot analysis revealed that PAK6 is highly expressed in testis and prostate tissues. Most importantly, immunofluorescence studies showed that PAK6 cotranslocates into the nucleus with AR in response to androgen. Transient transfection experiments showed that PAK6 specifically repressed AR-mediated transcription. This report identifies a novel function for a PAK-homologous protein and suggests a potential unique mechanism by which other signal transduction pathways may cross-talk with AR pathways to regulate AR function in normal and malignant prostate cells.

Pubmed ID: 11278661

Authors

  • Yang F
  • Li X
  • Sharma M
  • Zarnegar M
  • Lim B
  • Sun Z

Journal

The Journal of biological chemistry

Publication Data

May 4, 2001

Associated Grants

  • Agency: NCI NIH HHS, Id: CA70297
  • Agency: NIDDK NIH HHS, Id: DK 47636
  • Agency: NCI NIH HHS, Id: R01 CA070297
  • Agency: NCI NIH HHS, Id: R01 CA070297-06A1
  • Agency: NCI NIH HHS, Id: R01 CA070297-07
  • Agency: NCI NIH HHS, Id: R01 CA070297-08
  • Agency: NCI NIH HHS, Id: R01 CA070297-09
  • Agency: NCI NIH HHS, Id: R01 CA070297-10
  • Agency: NCI NIH HHS, Id: R01 CA070297-11A2
  • Agency: NCI NIH HHS, Id: R01 CA070297-12
  • Agency: NCI NIH HHS, Id: R01 CA087767
  • Agency: NCI NIH HHS, Id: R01 CA087767-01A2
  • Agency: NCI NIH HHS, Id: R01 CA087767-02
  • Agency: NCI NIH HHS, Id: R01 CA087767-03
  • Agency: NCI NIH HHS, Id: R01 CA087767-04
  • Agency: NCI NIH HHS, Id: R01 CA087767-05
  • Agency: NCI NIH HHS, Id: R01 CA151623
  • Agency: NIDDK NIH HHS, Id: R01 DK061002
  • Agency: NIDDK NIH HHS, Id: R01 DK061002-01A1
  • Agency: NIDDK NIH HHS, Id: R01 DK061002-02
  • Agency: NIDDK NIH HHS, Id: R01 DK061002-03
  • Agency: NIDDK NIH HHS, Id: R01 DK061002-04
  • Agency: NIDDK NIH HHS, Id: R01 DK061002-05
  • Agency: NCI NIH HHS, Id: R29 CA070297
  • Agency: NCI NIH HHS, Id: R29 CA070297-03
  • Agency: NCI NIH HHS, Id: R29 CA070297-04

Mesh Terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Cell Line
  • Humans
  • Molecular Sequence Data
  • Protein Binding
  • Protein-Serine-Threonine Kinases
  • Receptors, Androgen
  • Sequence Homology, Amino Acid
  • Transcriptional Activation
  • p21-Activated Kinases