Differential expression of the stress-associated proteins FKBP51 and FKBP52 in human and New World primate cells

The proteins FKBP51 and FK.BP52 are involved in regulation of the stress response due to their effects on the glucocorticoid receptor (GR) that binds Cortisol. FKBP51 and FKBP52 may occupy the same site in the GR complex. When FKBP52 is included in the complex, Cortisol responsiveness is enhanced. In contrast, the inclusion of FKBP51 inhibits Cortisol responsiveness. Therefore, the relative expression of these proteins partly determines cellular responsiveness to Cortisol. To begin to understand how these proteins are regulated, we have studied their gene expression in two cell lines, EBV-transformed squirrel monkey lymphoblasts (SML) and human lymphoblasts (HL), that exhibit different levels of the two proteins. The relative levels of FKBP51 and FKBP52 and their respective messenger RNAs were measured in SMLs and HLs. FKBP51 was 3.7-times higher in SMLs than in HLs, whereas FKBP52 in SMLs was 40% ofthat in HL. FKBP51 m RNA was 3.2-times higher in SML and FK.BP52 mRNA was 53% of that in HL. Our results show that the changes in mRNA and protein levels correspond, suggesting that mechanisms controlling mRNA levels are important for determining the overall proteins levels in the two cell lines. Understanding regulation of the levels of FKBP51 and FKBP52 may be important for glucocorticoid signaling dysfunction.