YEAST TOR (DRR) PROTEINS - AMINO-ACID-SEQUENCE ALIGNMENT AND IDENTIFICATION OF STRUCTURAL MOTIFS

被引：43
作者：
CAFFERKEY, R
MCLAUGHLIN, MM
YOUNG, PR
JOHNSON, RK
LIVI, GP
机构：
[1] SMITHKLINE BEECHAM PHARMACEUT,DEPT GENE EXPRESS SCI,KING OF PRUSSIA,PA 19406
[2] SMITHKLINE BEECHAM PHARMACEUT,DEPT BIOMOLEC DISCOVERY,KING OF PRUSSIA,PA 19406
[3] SMITHKLINE BEECHAM PHARMACEUT INC,DEPT MOLEC GENET,KING OF PRUSSIA,PA 19406
来源：
GENE | 1994年 / 141卷 / 01期
关键词：
RAPAMYCIN; SACCHAROMYCES CEREVISIAE; FKBP12; IMMUNOPHILINS; NUCLEAR LOCALIZATION SIGNALS;
D O I：
10.1016/0378-1119(94)90141-4
中图分类号：
Q3 [遗传学];
学科分类号：
071007 ; 090102 ;
摘要：
The yeast TOR1 (DRR1) and TOR2 (DRR2) proteins are putative targets of the immunosuppressive drug rapamycin (Rm), defined by dominant drug-resistance mutations. They share a large C-terminal domain that exhibits sequence similarity to the 110-kDa subunit of phosphatidylinositol (PI) 3-kinases. In this report, we present an amino acid (aa) sequence alignment of TOR1 (DRR1) and TOR2 (DRR2) and identify conserved and nonconserved motifs within the N-terminal domain that are indicative of possible nuclear localization. We also show that the mutations responsible for Rm resistance in four independent drr 2(dom) alleles alter the identical aa (Ser(1975)-->Arg) previously identified in drr1(dom) mutants (Ser(1972)-->Arg or Asn). Models for TOR (DRR) protein function are discussed.
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收藏
页码：133 / 136
页数：4
相关论文
共 20 条
[1]   DOMINANT MISSENSE MUTATIONS IN A NOVEL YEAST PROTEIN RELATED TO MAMMALIAN PHOSPHATIDYLINOSITOL 3-KINASE AND VPS34 ABROGATE RAPAMYCIN CYTOTOXICITY [J].
CAFFERKEY, R ;
YOUNG, PR ;
MCLAUGHLIN, MM ;
BERGSMA, DJ ;
KOLTIN, Y ;
SATHE, GM ;
FAUCETTE, L ;
ENG, WK ;
JOHNSON, RK ;
LIVI, GP .
MOLECULAR AND CELLULAR BIOLOGY, 1993, 13 (10) :6012-6023
[2]   ONCOGENES AND SIGNAL TRANSDUCTION [J].
CANTLEY, LC ;
AUGER, KR ;
CARPENTER, C ;
DUCKWORTH, B ;
GRAZIANI, A ;
KAPELLER, R ;
SOLTOFF, S .
CELL, 1991, 64 (02) :281-302
[3]   A COMPREHENSIVE SET OF SEQUENCE-ANALYSIS PROGRAMS FOR THE VAX [J].
DEVEREUX, J ;
HAEBERLI, P ;
SMITHIES, O .
NUCLEIC ACIDS RESEARCH, 1984, 12 (01) :387-395
[4]   FK-506-BINDING PROTEIN PROLINE ROTAMASE IS A TARGET FOR THE IMMUNOSUPPRESSIVE AGENT FK-506 IN SACCHAROMYCES-CEREVISIAE [J].
HEITMAN, J ;
MOVVA, NR ;
HIESTAND, PC ;
HALL, MN .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1991, 88 (05) :1948-1952
[5]  
HEITMAN J, 1992, NEW BIOL, V4, P448
[6]   TARGETS FOR CELL-CYCLE ARREST BY THE IMMUNOSUPPRESSANT RAPAMYCIN IN YEAST [J].
HEITMAN, J ;
MOVVA, NR ;
HALL, MN .
SCIENCE, 1991, 253 (5022) :905-909
[7]   THE 25-KDA FK506-BINDING PROTEIN IS LOCALIZED IN THE NUCLEUS AND ASSOCIATES WITH CASEIN KINASE-II AND NUCLEOLIN [J].
JIN, YJ ;
BURAKOFF, SJ .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (16) :7769-7773
[8]   REB1, A YEAST DNA-BINDING PROTEIN WITH MANY TARGETS, IS ESSENTIAL FOR CELL-GROWTH AND BEARS SOME RESEMBLANCE TO THE ONCOGENE MYB [J].
JU, QD ;
MORROW, BE ;
WARNER, JR .
MOLECULAR AND CELLULAR BIOLOGY, 1990, 10 (10) :5226-5234
[9]  
KENNELLY PJ, 1991, J BIOL CHEM, V266, P15555
[10]   RAPAMYCIN SENSITIVITY IN SACCHAROMYCES-CEREVISIAE IS MEDIATED BY A PEPTIDYL-PROLYL CIS-TRANS ISOMERASE RELATED TO HUMAN FK506-BINDING PROTEIN [J].
KOLTIN, Y ;
FAUCETTE, L ;
BERGSMA, DJ ;
LEVY, MA ;
CAFFERKEY, R ;
KOSER, PL ;
JOHNSON, RK ;
LIVI, GP .
MOLECULAR AND CELLULAR BIOLOGY, 1991, 11 (03) :1718-1723
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