GUANINE NUCLEOTIDE BINDING PROTEINS AS RECEPTOR-EFFECTOR COUPLERS

A family of guanine nucleotide binding proteins (G-proteins) functions in transmembrane signalling as receptor-effector couplers. G proteins couple to a diverse array of receptors including those for hormones, neurotransmitters, light, odorants, and certain growth factors. Effector functions regulated (positively and, in some instances, negatively) by G-proteins include cAMP formation, phosphoinositide breakdown, potassium an calcium channels, and cGMP degradation. We have used a variety of techniques to study the expression, distribution, regulation, structure and function of G-proteins. Our studies highlight the diversity within the G-protein family. We have purified novel G-proteins and using cloned cDNAs, defined their primary structure and distribution. We have demonstrated developmental and differentiation-dependent regulation of G protein synthesis. Using peptide specific antibodies, in situ hybridization and northern analyses, and protein reconstitution techniques, we have defined the specificity of G-proteins in coupling to receptors and effectors. These studies provide the basis for understanding the role of G-proteins in normal signal transduction and for elucidating possible defects in G-protein structure or function as the basis for abnormal signal transduction.