Abstract
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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 15345-15353 |
| Number of pages | 9 |
| Journal | Journal of Biological Chemistry |
| Volume | 276 |
| Issue number | 18 |
| DOIs | |
| State | Published - May 4 2001 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Biochemistry
Cite this
Androgen Receptor Specifically Interacts with a Novel p21-activated Kinase, PAK6. / Yang, Fajun; Li, Xiaoyu; Sharma, Manju; Zarnegar, Mark; Lim, Bing; Sun, Zijie.
In: Journal of Biological Chemistry, Vol. 276, No. 18, 04.05.2001, p. 15345-15353.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Androgen Receptor Specifically Interacts with a Novel p21-activated Kinase, PAK6
AU - Yang, Fajun
AU - Li, Xiaoyu
AU - Sharma, Manju
AU - Zarnegar, Mark
AU - Lim, Bing
AU - Sun, Zijie
PY - 2001/5/4
Y1 - 2001/5/4
N2 - 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.
AB - 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.
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U2 - 10.1074/jbc.M010311200
DO - 10.1074/jbc.M010311200
M3 - Article
VL - 276
SP - 15345
EP - 15353
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 18
ER -