國家衛生研究院 NHRI:Item 3990099045/2129

NHRI > Institute of Biotechnology and Pharmaceutical Research > Hua-Chien Chen(1997-2001) > Periodical Articles > Item 3990099045/2129

Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/2129

Title:	Identification of human male germ cell-associated kinase, a kinase transcriptionally activated by androgen in prostate cancer cells
Authors:	Xia, L;Robinson, D;Ma, AH;Chen, HC;Wu, F;Qiu, Y;Kung, HJ
Contributors:	Institute of Biotechnology and Pharmaceutical Research
Abstract:	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 5alpha-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 prouct 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.
Keywords:	Biochemistry & Molecular Biology
Date:	2002-09-20
Relation:	Journal of Biological Chemistry. 2002 Sep;277(38):35422-35433.
Link to:	http://dx.doi.org/10.1074/jbc.M203940200
JIF/Ranking 2023:	http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1083-351X&DestApp=IC2JCR
Cited Times(WOS):	https://www.webofscience.com/wos/woscc/full-record/WOS:000178117000098
Cited Times(Scopus):	http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=0037144418
Appears in Collections:	[Hua-Chien Chen(1997-2001)] Periodical Articles

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