Tissue distribution and abundance of human FKBP51, an FK506-binding protein that can mediate calcineurin inhibition

被引:103
作者
Baughman, G
Wiederrecht, GJ
Chang, F
Martin, MM
Bourgeois, S
机构
[1] SALK INST BIOL STUDIES,REGULATORY BIOL LAB,SAN DIEGO,CA 92186
[2] MERCK & CO INC,MERCK SHARP & DOHME RES LABS,DEPT IMMUNOL RES,RAHWAY,NJ 07065
关键词
D O I
10.1006/bbrc.1997.6307
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
We previously described the isolation of an FK506-binding protein, FKBP51, that is predominantly expressed in murine T cells and is capable of mediating drug-dependent calcineurin inhibition in vitro. In addition, the gene for FKBP51 is induced by glucocorticoids. Screening of a human thymus cDNA library resulted in the identification of the human homologue of FKBP51. Expression of the 3.7 kb mRNA corresponding to FKBP51 is induced by glucocorticoids in the human T cell line, C7TK.4. The 51.2 kDa protein encoded by this gene shares 87% identity to murine FKBP51 and demonstrates a similar IC50 value for the FK506-mediated inhibition of calcineurin phosphatase in vitro. The distribution and abundance of FKBP51 and FKBP12 in seventeen human tissues were compared by Western analysis. Unlike its murine counterpart, the human FKBP51 is abundantly expressed in numer ous tissues and in many cases, is in molar excess over FKBP12. (C) 1997 Academic Press.
引用
收藏
页码:437 / 443
页数:7
相关论文
共 31 条
[1]   Immunopharmacology of rapamycin [J].
Abraham, RT ;
Wiederrecht, GJ .
ANNUAL REVIEW OF IMMUNOLOGY, 1996, 14 :483-510
[2]  
ALTSCHUL SF, 1990, J MOL BIOL, V215, P403, DOI 10.1006/jmbi.1990.9999
[3]  
BAUGHMAN G, 1995, MOL CELL BIOL, V15, P4395
[4]   GENES NEWLY IDENTIFIED AS REGULATED BY GLUCOCORTICOIDS IN MURINE THYMOCYTES [J].
BAUGHMAN, G ;
HARRIGAN, MT ;
CAMPBELL, NF ;
NURRISH, SJ ;
BOURGEOIS, S .
MOLECULAR ENDOCRINOLOGY, 1991, 5 (05) :637-644
[5]  
BECKER JW, 1993, J BIOL CHEM, V268, P11335
[6]   CYCLOSPORINE-A AND FK506 - MOLECULAR MECHANISMS OF IMMUNOSUPPRESSION AND PROBES FOR TRANSPLANTATION BIOLOGY [J].
BIERER, BE ;
HOLLANDER, G ;
FRUMAN, D ;
BURAKOFF, SJ .
CURRENT OPINION IN IMMUNOLOGY, 1993, 5 (05) :763-773
[7]   PROBING IMMUNOSUPPRESSANT ACTION WITH A NONNATURAL IMMUNOPHILIN LIGAND [J].
BIERER, BE ;
SOMERS, PK ;
WANDLESS, TJ ;
BURAKOFF, SJ ;
SCHREIBER, SL .
SCIENCE, 1990, 250 (4980) :556-559
[8]  
BRADFORD MM, 1976, ANAL BIOCHEM, V72, P248, DOI 10.1016/0003-2697(76)90527-3
[9]   IDENTIFICATION OF THE IMMUNOPHILINS CAPABLE OF MEDIATING INHIBITION OF SIGNAL-TRANSDUCTION BY CYCLOSPORINE-A AND FK506 - ROLES OF CALCINEURIN BINDING AND CELLULAR LOCATION [J].
BRAM, RJ ;
HUNG, DT ;
MARTIN, PK ;
SCHREIBER, SL ;
CRABTREE, GR .
MOLECULAR AND CELLULAR BIOLOGY, 1993, 13 (08) :4760-4769
[10]   SINGLE-STEP METHOD OF RNA ISOLATION BY ACID GUANIDINIUM THIOCYANATE PHENOL CHLOROFORM EXTRACTION [J].
CHOMCZYNSKI, P ;
SACCHI, N .
ANALYTICAL BIOCHEMISTRY, 1987, 162 (01) :156-159