Pertussis Toxin-sensitive GTP-binding Proteins in Neuronal Tissues: Recent Insights into Expression and Function
Receptors which identify neurotransmitters, hormones and growth factors can be subdivided into three broad classes. These are (1) receptors which allow direct gating of ions; (2) receptors which indirectly control the activity of effector systems which are either ion channels or enzymes which generate intracellular second messengers; and (3) receptors which express tyrosyl kinase activity. This review will focus on the mechanism of action of the second class of receptors, because in every case receptor control of effector function is absolutely dependent upon the intermediate activation of one or more members of a family of highly homologous guanine nucleotide-binding proteins (G-proteins). G-proteins which are implicated in cellular signalling processes are found widely throughout evolution. Highly conserved G-proteins have been identified either via cDNA cloning or immunological means in each of mammals, birds, amphibia, invertebrates, yeast and slime moulds. Preliminary evidence has also been presented to indicate the expression of related proteins in both green plants and bacteria. It should be remembered however that not all proteins which bind and hydrolyse GTP are likely to be involved in cellular signalling processes. For example, factors involved in protein synthesis initiation and elongation require GTP, as do the α- and β-subunits of the microtubule-forming protein, tubulin. Further, a series of low-Mr (21-28 kDa), GTP-utilizing polypeptides have been identified, including members of the ras, ral, rho, ARF and smg families of proteins. A number of these proteins have been implicated in signalling processes, particularly in relation to the control of mitogenesis, but further roles, especially in relation to control of secretory processes, appear likely, particularly when genetic information from yeast systems is taken into consideration.
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