G proteins as drug targets

被引:61
作者
Höller, C [1 ]
Freissmuth, M [1 ]
Nanoff, C [1 ]
机构
[1] Univ Vienna, Inst Pharmacol, A-1090 Vienna, Austria
关键词
G protein subunits; modified guanine nucleotides; receptor-derived peptides; mastoparan and related venoms; suramin analogues; amphiphilic cations;
D O I
10.1007/s000180050288
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 structure and function of heterotrimeric G protein subunits is known in considerable detail. Upon stimulation of a heptahelical receptor by the appropriate agonists, the cognate G proteins undergo a cycle of activation and deactivation; the alpha-subunits and the beta gamma-dimers interact sequentially with several reaction partners (receptor, guanine nucleotides and effecters as well as regulatory proteins) by exposing appropriate binding sites. For most of these domains, low molecular weight ligands have been identified that either activate or inhibit signal transduction. These ligands include short peptides derived from receptors, G protein subunits and effecters, mastoparan and related insect venoms, modified guanine nucleotides, suramin analogues and amphiphilic cations. Because compounds that act on G proteins may be endowed with new forms of selectivity, we propose that G protein subunits may therefore be considered as potential drug targets.
引用
收藏
页码:257 / 270
页数:14
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共 150 条
  • [11] BERTIN B, 1992, J BIOL CHEM, V267, P8200
  • [12] NATURAL POLYAMINES STIMULATE G-PROTEINS
    BUEB, JL
    DASILVA, A
    MOUSLI, M
    LANDRY, Y
    [J]. BIOCHEMICAL JOURNAL, 1992, 282 : 545 - 550
  • [13] Pharmacology of muscarinic receptor subtypes constitutively activated by G proteins
    Burstein, ES
    Spalding, TA
    Brann, MR
    [J]. MOLECULAR PHARMACOLOGY, 1997, 51 (02) : 312 - 319
  • [14] DIFFERENTIAL-EFFECTS OF SURAMIN ON THE COUPLING OF RECEPTORS TO INDIVIDUAL-SPECIES OF PERTUSSIS-TOXIN-SENSITIVE GUANINE-NUCLEOTIDE-BINDING PROTEINS
    BUTLER, SJ
    KELLY, ECH
    MCKENZIE, FR
    GUILD, SB
    WAKELAM, MJO
    MILLIGAN, G
    [J]. BIOCHEMICAL JOURNAL, 1988, 251 (01) : 201 - 205
  • [15] ISOZYME-SELECTIVE STIMULATION OF PHOSPHOLIPASE C-BETA-2 BY G-PROTEIN BETA-GAMMA-SUBUNITS
    CAMPS, M
    CAROZZI, A
    SCHNABEL, P
    SCHEER, A
    PARKER, PJ
    GIERSCHIK, P
    [J]. NATURE, 1992, 360 (6405) : 684 - 686
  • [16] STIMULATION OF PHOSPHOLIPASE-C BY GUANINE-NUCLEOTIDE-BINDING PROTEIN-BETA-GAMMA SUBUNITS
    CAMPS, M
    HOU, CF
    SIDIROPOULOS, D
    STOCK, JB
    JAKOBS, KH
    GIERSCHIK, P
    [J]. EUROPEAN JOURNAL OF BIOCHEMISTRY, 1992, 206 (03): : 821 - 831
  • [17] Drugs interacting with G protein α subunits:: selectivity and perspectives
    Chahdi, A
    Daeffler, L
    Gies, JP
    Landry, Y
    [J]. FUNDAMENTAL & CLINICAL PHARMACOLOGY, 1998, 12 (02) : 121 - 132
  • [18] A truncated form of RGS3 negatively regulates G protein-coupled receptor stimulation of adenylyl cyclase and phosphoinositide phospholipase C
    Chatterjee, TK
    Eapen, AK
    Fisher, RA
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (24) : 15481 - 15487
  • [19] A REGION OF ADENYLYL-CYCLASE-2 CRITICAL FOR REGULATION BY G-PROTEIN BETA-GAMMA-SUBUNITS
    CHEN, JQ
    DEVIVO, M
    DINGUS, J
    HARRY, A
    LI, JR
    SUI, JL
    CARTY, DJ
    BLANK, JL
    EXTON, JH
    STOFFEL, RH
    INGLESE, J
    LEFKOWITZ, RJ
    LOGOTHETIS, DE
    HILDEBRANDT, JD
    IYENGAR, R
    [J]. SCIENCE, 1995, 268 (5214) : 1166 - 1169
  • [20] Rethinking receptor-G protein-effector interactions
    Chidiac, P
    [J]. BIOCHEMICAL PHARMACOLOGY, 1998, 55 (05) : 549 - 556