23] Identification of mutant forms of G-protein α subunits in human neoplasia by polymerase chain reaction-based techniques

Abstract

Publisher Summary G-protein α subunits bind guanosine-5'-triphosphate (GTP) and guanosine-diphosphate (GDP) and cycle between an inactive GDP-bound form and an active GTP-bound form. The role of α subunits in signal transduction may be defined genetically and biochemically, when a G-protein α subunit is expressed in a given cell type, it may interact with an appropriate set of activated receptors (G-protein receptors), bind GTP for GDP, and transduce its signal to second messengers via a relatively slow intrinsic hydrolysis of GTP to GDP, thereby instigating a complex sorting and amplification cascade resulting, finally, in either mitogenic effects, hormone secretion, or cell differentiation. Members of the α-subunit families may be divided into four different groups based on amino acid sequences. In the first group the αs and the olfactory subunits activate adenylyl cyclase and elevate levels of cAMP within the cell. The α subunits of the inhibitory class are largely ADP-ribosylated by pertussis toxin and include Gi1, Gi2, Gi3, Go, and transducin. ADP-ribosylation at the carboxyl terminus by pertussis toxin results in the modification of amino acid sequences in the α chain and uncouples the α subunit from its receptor and, consequently, from its signal transduction pathway. A further group of α subunits has been cloned, the Gq class. This group of α subunits activates phospholipase C and is pertussis toxin insensitive. A fourth group, consisting of Gα12 and Gα13, has been cloned, and their sequences have been shown to be unique from the other three groups.