Identification of human male germ cell-associated kinase, a kinase transcriptionally activated by androgen in prostate cancer cells

Liang Xia, Dan Robinson, Ma Ai-Hong, Hua Chien Chen, Frederick Wu, Yun Qiu, Hsing Jien Kung

研究成果: 雜誌貢獻文章同行評審

31 引文 斯高帕斯(Scopus)


Androgen is involved in both normal development and malignant transformation of prostate cells. The signal transduction pathways associated with these processes are not well understood. Using a novel kinase display approach, we have identified a protein kinase, human male germ cell-associated kinase (hMAK), which is transcriptionally induced by the androgenic hormone 5α-dihydrotestosterone (DHT). The kinetics of induction is rapid and dose-dependent, and the induction is not blocked by cycloheximide treatment. Real time reverse transcription-PCR studies demonstrated a 9-fold induction of hMAK by 10 nM DHT at 24 h post-stimulation. The expression levels of hMAK in prostate cancer cell lines are in general higher than those of normal prostate epithelial cells. A reverse transcription-PCR product encompassing the entire hMAK open reading frame was isolated. The results from sequencing analysis showed that the hMAK protein is 623 amino acids in length and contains a kinase catalytic domain at its N terminus, followed by a proline/glutamine-rich domain. The catalytic domain of this kinase contains sequence motifs related to both the cyclin-dependent kinase and the mitogen-activated protein kinase families. When expressed in COS1 cells, hMAK is kinase-active as demonstrated by autophosphorylation and phosphorylation of exogenous substrate and is localized in the nucleus. A 3.7-kilobase pair promoter of the hMAK locus was isolated from a human genomic DNA bacterial artificial chromosome clone and was shown to be activated by DHT. This activation can be blocked by an anti-androgen drug bicalutamide (Casodex), implicating the involvement of androgen receptor in this process. Taken together, these data suggest that hMAK is a protein kinase targeted by androgen that may participate in androgen-mediated signaling in prostate cancer cells.
頁(從 - 到)35422-35433
期刊Journal of Biological Chemistry
出版狀態已發佈 - 9月 20 2002

ASJC Scopus subject areas

  • 生物化學
  • 分子生物學
  • 細胞生物學


深入研究「Identification of human male germ cell-associated kinase, a kinase transcriptionally activated by androgen in prostate cancer cells」主題。共同形成了獨特的指紋。