G-Protein Subunit Lipidation in Membrane Association and Signaling

  • J. A. Thissen
  • P. J. Casey
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 108 / 2)


The heterotrimeric GTP-binding proteins (G-proteins), comprised of α, β, and γ subunits, are localized to the inner surface of the plasma membrane where they serve as receptor-mediated signal transducers. It is the α subunit, which exists as many different subtypes, that confers identity to the oligomer and in most systems governs the specificity of the interaction with receptor and effector. The βγ subunits, of which multiple forms also exist, appear to function as a complex, and individual forms may be shared among the multiple α subunits (Roof et al. 1985; Fung 1983; Robishaw et al. 1989; Schmidt and Neer 1991; Tamir et al. 1991). A model for G-protein signal transduction is described in Fig. 1. Receptor-mediated activation of the G-protein results in the exchange of GTP for GDP on the α subunit, promoting its separation from βγ. Subsequent interaction with a membrane-associated effector protein in turn generates an intracellular response. The model depicted in Fig. 1 shows the α subunit interacting with the effector protein, as most available evidence points to the GTP-bound form of the α subunit as activating effectors such as adenylyl cyclase, retinal phosphodiesterase, and a phosphoinositide-specific phospholipase C (Northup et al. 1983; Katada et al. 1984; Cerione et al. 1988; Robishaw et al. 1986; Smrcka et al. 1991). However, recent evidence has indicated that the βγ complex may play a more direct role in G-protein-linked signal transduction than previously thought (Gilman 1987; Kim et al. 1989; Tang and Gilman 1991; Whiteway et al. 1989). This has been most clearly demonstrated in the mating factor signaling pathway in yeast (Whiteway et al. 1989, and references therein).


Myristic Acid Membrane Association Prenyl Diphosphate Myristoyl Group Farnesyl Group 
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© Springer-Verlag Berlin Heidelberg 1993

Authors and Affiliations

  • J. A. Thissen
  • P. J. Casey

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