INHIBITION OF CALCINEURIN BY CYCLOSPORINE-A CYCLOPHILIN REQUIRES CALCINEURIN-B

被引：53

作者：

HADDY, A ^{[1
]}

SWANSON, SKH ^{[1
]}

BORN, TL ^{[1
]}

RUSNAK, F ^{[1
]}

机构：

[1] MAYO CLIN & MAYO FDN,HEMATOL RES SECT,ROCHESTER,MN 55905

来源：

FEBS LETTERS | 1992年 / 314卷 / 01期

关键词：

CALCINEURIN; CYCLOSPORINE-A; CYCLOPHILIN; IMMUNOSUPPRESSION;

D O I：

10.1016/0014-5793(92)81456-V

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：

The interaction of the immunosuppressive complex cyclosporin A-cyclophilin (CsA-CyP) with the Ca2+/calmodulin-dependent protein phosphatase calcineurin is investigated using a recombinant form of the A subunit of calcineurin (rCNA). Only in the presence of purified calcineurin B (CNB) does rCNA show the response of native calcineurin, i.e. 50% inhibition of rCNA phosphatase activity at 6 nM human cyclophilin B and 0.6 muM human cyclophilin A using [P-32]casein as substrate, yet stimulation of activity with p-nitrophenyl phosphate as substrate. This study demonstrates that the B subunit is necessary to confer sensitivity of calcineurin to CsA-CyP.

引用

页码：37 / 40

页数：4

共 33 条

[1] IDENTIFICATION OF CALCINEURIN AS A KEY SIGNALING ENZYME IN LYMPHOCYTE-T ACTIVATION [J].

CLIPSTONE, NA ;

CRABTREE, GR .

NATURE, 1992, 357 (6380) :695-697

[2] THE STRUCTURE AND REGULATION OF PROTEIN PHOSPHATASES [J].

COHEN, P .

ANNUAL REVIEW OF BIOCHEMISTRY, 1989, 58 :453-508

[3] INDUCTION OF INTERLEUKIN-2 MESSENGER-RNA INHIBITED BY CYCLOSPORIN-A [J].

ELLIOTT, JF ;

LIN, YA ;

MIZEL, SB ;

BLEACKLEY, RC ;

HARNISH, DG ;

PAETKAU, V .

SCIENCE, 1984, 226 (4681) :1439-1441

[4]

FRUMAN DA, 1992, P NATL ACAD SCI USA, V89, P3689

[5]

GUERINI D, 1991, ADV PROT PHOSPHATASE, V6, P391

[6] RESOLUTION OF BOVINE BRAIN CALCINEURIN SUBUNITS - STIMULATORY EFFECT OF SUBUNIT-B ON SUBUNIT-A PHOSPHATASE-ACTIVITY [J].

GUPTA, RC ;

KHANDELWAL, RL ;

SULAKHE, PV .

FEBS LETTERS, 1985, 190 (01) :104-108

[7] CYCLOPHILIN - A SPECIFIC CYTOSOLIC BINDING-PROTEIN FOR CYCLOSPORIN-A [J].

HANDSCHUMACHER, RE ;

HARDING, MW ;

RICE, J ;

DRUGGE, RJ .

SCIENCE, 1984, 226 (4674) :544-547

[8]

HARDING MW, 1986, J BIOL CHEM, V261, P8547

[9] A RECEPTOR FOR THE IMMUNOSUPPRESSANT FK506 IS A CIS-TRANS PEPTIDYL-PROLYL ISOMERASE [J].

HARDING, MW ;

GALAT, A ;

UEHLING, DE ;

SCHREIBER, SL .

NATURE, 1989, 341 (6244) :758-760

[10] THE MECHANISM OF ACTION OF THE IMMUNOSUPPRESSIVE DRUG FK-506 [J].

KAY, JE ;

DOE, SEA ;

BENZIE, CR .

CELLULAR IMMUNOLOGY, 1989, 124 (01) :175-181

← 1 2 3 4 →