Guanine nucleotide-binding proteins involved in transmembrane signaling.

Transmission of signals from a hormone-receptor complex to a number of intracellular effectors is mediated by a family of guanine nucleotide-binding proteins (G proteins). Each G protein consists of an alpha, beta, and gamma subunit and is most clearly distinguished from other G proteins by the biological and biochemical attributes of its GTP-binding alpha subunit. The alpha proteins can be divided into general classes by their susceptibility to modification by the bacterial toxins, cholera toxin, and pertussis toxin. In brain, there are three substrates for ADP-ribosylation by pertussis toxin with molecular weights of 41,000 (alpha 41), 40,000 (alpha 40) and 39,000 (alpha 39). The alpha 39 is the most abundant. We purified the alpha 41 and alpha 39 proteins from bovine brain and have used immunologic and biochemical tools to compare their structure and function. We have also isolated and characterized a cDNA clone from a bovine pituitary library that encodes alpha 41. The deduced amino acid sequence of the alpha 41 clone demonstrates marked homology to several other GTP-binding proteins. Southern blot analysis of the cloned alpha 41 cDNA suggests the presence of two genes encoding this G protein. In addition, we identified a cDNA clone for a novel, putative G protein, alpha h, which demonstrates marked sequence homology with other G proteins but which represents a clearly distinct gene product. Taken together, these data suggest a new level of complexity in the organization of the G protein supergene family, with multiple G proteins of similar overall structural and mechanistic properties likely to be identified as products of distinct genes.