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
相关论文
共 150 条
  • [41] HAGELUKEN A, 1995, MOL PHARMACOL, V47, P234
  • [42] LIPOPHILIC BETA-ADRENOCEPTOR ANTAGONISTS AND LOCAL-ANESTHETICS ARE EFFECTIVE DIRECT ACTIVATORS OF G-PROTEINS
    HAGELUKEN, A
    GRUNBAUM, L
    NURNBERG, B
    HARHAMMER, R
    SCHUNACK, W
    SEIFERT, R
    [J]. BIOCHEMICAL PHARMACOLOGY, 1994, 47 (10) : 1789 - 1795
  • [43] The β2-adrenergic receptor interacts with the Na+/H+-exchanger regulatory factor to control Na+/H+ exchange
    Hall, RA
    Premont, RT
    Chow, CW
    Blitzer, JT
    Pitcher, JA
    Claing, A
    Stoffel, RH
    Barak, LS
    Shenolikar, S
    Weinman, EJ
    Grinstein, S
    Lefkowitz, RJ
    [J]. NATURE, 1998, 392 (6676) : 626 - 630
  • [44] SITE OF G-PROTEIN BINDING TO RHODOPSIN MAPPED WITH SYNTHETIC PEPTIDES FROM THE ALPHA-SUBUNIT
    HAMM, HE
    DERETIC, D
    ARENDT, A
    HARGRAVE, PA
    KOENIG, B
    HOFMANN, KP
    [J]. SCIENCE, 1988, 241 (4867) : 832 - 835
  • [45] HAWES BE, 1994, J BIOL CHEM, V269, P29825
  • [46] PHOSDUCIN INHIBITS RECEPTOR PHOSPHORYLATION BY THE BETA-ADRENERGIC-RECEPTOR KINASE IN A PKA-REGULATED MANNER
    HEKMAN, M
    BAUER, PH
    SOHLEMANN, P
    LOHSE, MJ
    [J]. FEBS LETTERS, 1994, 343 (02) : 120 - 124
  • [47] RGS4 and GAIP are GTPase-activating proteins for G(q alpha) and block activation of phospholipase C beta by gamma-thio-GTP-G(q alpha)
    Hepler, JR
    Berman, DM
    Gilman, AG
    Kozasa, T
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (02) : 428 - 432
  • [48] G-PROTEINS
    HEPLER, JR
    GILMAN, AG
    [J]. TRENDS IN BIOCHEMICAL SCIENCES, 1992, 17 (10) : 383 - 387
  • [49] Modulation of Ca2+ channels by G-protein beta gamma subunits
    Herlitze, S
    Garcia, DE
    Mackie, K
    Hille, B
    Scheuer, T
    Catterall, WA
    [J]. NATURE, 1996, 380 (6571) : 258 - 262
  • [50] Molecular determinants of inactivation and G protein modulation in the intracellular loop connecting domains I and II of the calcium channel alpha(1A) subunit
    Herlitze, S
    Hockerman, GH
    Scheuer, T
    Catterall, WA
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (04) : 1512 - 1516