THE ROLE of heterotrimeric guanine nucleotide binding proteins (G proteins) in signal transduction was first covered in Endocrine Reviews in 1981, when three distinct G proteins involved in visual transduction and regulation of cAMP formation were recognized (1). This topic was updated in Endocrine Reviews in 1989 by which time the number of mammalian G proteins identified had doubled, and their roles in regulation of various phospholipases and ion channels had been recognized (2). Barely 3 years later, the number of distinct mammalian G proteins recognized has again doubled, multiple G proteins have been identified in invertebrates, plants, and single-celled eukaryotes, and the number of cellular functions shown to be regulated by G proteins has increased correspondingly. Numerous excellent reviews covering various aspects of this topic have recently appeared (3–9), but given the rapidity of progress in this field, an update in Endocrine Reviews appears timely.

This review summarizes recent progress in our understanding of G protein structure, function, and diversity. Particular emphasis is given to the problem of defining specificity in coupling of receptors to various G proteins, and the involvement of abnormal G proteins in human disease. Two related areas, that of G protein-coupled receptors (10) and of low molecular weight GTP-binding proteins such as the ras p21 protooncogenes (7, 11, 12), have also undergone an explosive increase in information. Detailed consideration of the structure, function, and diversity of both of these important classes of protein beyond the scope of this review, but selected areas will covered as they relate to the heterotrimeric G proteins themselves. Our citation of the extensive literature on G proteins is not comprehensive; instead, we have emphasized more recent references, and in some instances directed the reader to recent reviews for more detailed coverage of a particular area.