PKA-Mediated Regulation of B/K Gene Transcription in PC12 Cells
PKA-Mediated Regulation of B/K Gene Transcription in PC12 Cells
- Mi-Hyun Choi Ho-Shik Kim Sung-Ho Choi Mi-Young Kim Yoon-Seong Jang Young-Min Jang Jeong-Hwa Lee Seon
- 대한생리학회-대한약리학회
- The Korean Journal of Physiology & Pharmacology
- 제9권 제6호
- 등재여부 : KCI등재
- 2005.01
- 333 - 340 (8 pages)
B/K protein is a novel protein containing double C2-like domains. We examined the specific signaling pathway that regulates the transcription of B/K in PC12 cells. When the cells were treated with forskolin (50μM), B/K mRNA and protein levels were time-dependently decreased, reaching the lowest level at 3 or 4 hr, and thereafter returning to the control level. Chemicals such as dibutyryl-cAMP, cell- permeable cyclic AMP (cAMP) analogue and CGS21680, adenosine receptor A<SUB>2A</SUB> agonist, also repressed the B/K transcription. However, 1,9-dideoxyforskolin did not show inhibitory effect on B/K transcription, suggesting direct involvement of cAMP in the forskolin-induced inhibition of B/K transcription. Effect of forskolin, dibutyryl cAMP and CGS21680 was significantly reduced in PKA-deficient PC12 cell line (PC12-123.7). One cAMP-response element (CRE)-like sequence (B/K CLS) was found in the promoter region of B/K DNA, and electrophoretic mobility shift assay indicated its binding to CREM and CREB. Forskolin significantly suppressed the promoter activity in CHO-K1 cells transfected with the constructs containing B/K CLS, but not with the construct in which B/K CLS was mutated (AC:TG). Taken together, we suggest that the transcription of B/K gene in PC12 cells may be regulated by PKA-dependent mechanism.