Suppression of androgen receptor transactivation by Pyk2 via interaction and phosphorylation of the ARA55 coregulator

Xin Wang, Yue Yang, Xiaojian Guo, Erik R. Sampson, Cheng Lung Hsu, Meng Yin Tsai, Shuyuan Yeh, Guan Wu, Yinglu Guo, Chawnshang Chang

Research output: Contribution to journalArticlepeer-review

46 Scopus citations

Abstract

The proline-rich tyrosine kinase 2 (Pyk2) was first identified as a key kinase linked to the MAP kinase and JNK signaling pathways that play important roles in cell growth and adhesion. The linkage between Pyk2 and the androgen receptor (AR), an important transcription factor in prostate cancer progression, however, remains unclear. Here we report that using the full-length androgen receptor-associated protein, ARA55, coregulator as bait, we were able to isolate an ARA55-interacting protein, Pyk2, and demonstrated that Pyk2 could repress AR transactivation via inactivation of ARA55. This inactivation may result from the direct phosphorylation of ARA55 by Pyk2 at tyrosine 43, impairing the coactivator activity of ARA55 and/or sequestering ARA55 to reduce its interaction with AR. Our finding that Pyk2 can indirectly modulate AR function via interaction and/or phosphorylation of ARA55 not only expands the role of Pyk2 in AR-mediated prostate cancer growth but also strengthens the role of ARA55 as an AR coregulator.

Original languageEnglish (US)
Pages (from-to)15426-15431
Number of pages6
JournalJournal of Biological Chemistry
Volume277
Issue number18
DOIs
StatePublished - May 3 2002

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