G Proteins: Transducers of Receptor-Generated Signals

The role of G proteins in transmembrane signalling

“…The G proteins that transmit information from receptors to their intracellular effector systems belong to a large homologous family of trimeric proteins each with an a subunit that binds guanine nucleotides, and ft and y subunits that are always tightly associated (Casperson & Bourne, 1987;Gilman, 1987;Holbrook & Kim, 1989). Different G proteins are most readily distinguished by their a subunits, though there are also more subtle structural and functional differences in some ft and y subunits (Cerione et al, 1987) (Table 1).…”

“…Recognition of the latter appears to involve both the loop that links the fifth and sixth transmembrane regions and part of the C-terminal tail (Kubo et al, 1988;Kobilka et al, 1988;O'Dowd et al, 1989) with positively charged residues perhaps playing a major role (Ross, 1989;Huang et al, 1990) Table summarizes properties of only those G proteins which have been both isolated and for which a function is known (Gilman, 1987;Lochrie & Simon, 1988;Jones et al, 1990). There are many other a subunits with unknown functions and many signalling pathways are known to involve as yet unidentified G proteins.…”

“…2. GDP bound to the G protein a subunit normally dissociates only slowly (half time of 1-5 min for G. and of hours for transducin) (Brandt & Ross, 1985;Gilman, 1987;Stryer, 1988;Chabre & Deterre, 1989), but the concerted actions of intracellular Mg2+ and activated receptors catalyse G protein activation by increasing the rate of GDP dissociation from the a subunit and its replacement by GTP. A useful pharmacological tool is the AIF4-complex which circumvents the need for GDP dissociation by binding alongside GDP and mimicking the terminal phosphate group of GTP, thereby promoting G protein activation (Bigay et al, 1985).…”

“…Indeed, a single fly complex can recycle between a subunits, allowing many to be activated by a single bleached rhodopsin (Fung, 1983). Other G proteins, after detergent solubilization, behave in a similar way to transducin: GTPyS promotes G protein dissociation whereas GDP stabilizes the oligomeric form (Higashijima et al, 1987;Gilman, 1987), a-GDP binds more tightly than a-GTP to a fly affinity column (Pang & Sternweis, 1989), and in membrane preparations GTPyS or GTP with hormone cause dissociation of a and fly subunits (Iyengar et al, 1988;Ransnas et al, 1989). In view of the suggestion that fly subunits mediate hormonal inhibition of adenylate cyclase by binding to active as-GTP (Katada et al, 1984) (see below), it is noteworthy that active a subunits bind with different affinities to the same fly complexes: ac-GTP, for example, binds more tightly than ac-GTP to fly (Sternweis, 1986;Pang & Sternweis, 1989).…”

“…The developments that followed Rodbell's pioneering studies have established that many different receptors regulate many intracellular effectors through a family of closely related G proteins (Citri & Schramm, 1980;Rodbell, 1980;Schramm & Selinger, 1984;Northup, 1985;Levitzki, 1988). Many excellent recent reviews have focused on various aspects of these interactions between receptors, G proteins and intracellular effectors (Casperson & Bourne, 1987;Gilman, 1987;Allende, 1988;Lochrie & Simon, 1988;Weiss et al, 1988;Chabre & Deterre, 1989;Ross, 1989;Houslay, 1990).…”