Site‐selective cAMP analogs induce nuclear translocation of the RII cAMP receptor protein in Ha‐MuSV‐transformed NIH/3T3 cells

FEBS Letters

Clair, Timothy²  Ally, Shamsia²  Robins, Roland K.¹  Tagliaferri, Pierosandro²  Sang Cho-Chung, Yoon² 

[1] Nucleic Acid Research Institute, Costa Mesa, CA 92626, USA;Cellular Biochemistry Section, Laboratory of Tumor Immunology and Biology, National Cancer Institute, NIH, Bethesda, MD 20892 USA

关键词: cAMP;    Protein kinase;    Reverse transformation;   

DOI  :  10.1016/0014-5793(87)80488-X

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Site-selective cAMP analogs, depending on the position of their substituents on the adenine ring, selectively bind to either site 1 or site 2 of the known cAMP binding sites of protein kinase. Treatment of Harvey murine sarcoma virus-transformed NIH/3T3 cells with such site-selective analogs results in growth inhibition and phenotypic reversion, and the combination of a C-8 thio or halogen analog (site 1 selective) with an N ⁶ analog (site 2 selective) produces a synergistic effect. We report here that the growth inhibitory effect of the analogs correlates with the nuclear translocation of the R^II cAMP receptor protein, the regulatory subunit of protein kinase type it. The transformed NIH/3T3 cells contained no detectable level of R^II in the nucleus, whereas nontransformed NIH/3T3 cells exhibited a high level of nuclear R^II. Within 30 min after treatment of the transformed cells with the site-selective analogs, immunofluorescence against the R^II protein markedly increased in the cell nucleus. The nuclear translocation of the R^II cAMP receptor protein is an early event in the reverse transformation of the fibroblasts treated with site-selective cAMP analogs.

【 授权许可】

Unknown