GUANINE NUCLEOTIDE BINDING PROTEINS AS RECEPTOR-EFFECTOR COUPLERS

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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 and 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. Using peptide specific antibodies, we have defined the specificity of G-proteins in coupling to receptors and effectors. We have created mutations in alpha subunits that cause constitutive activation, and transfected these into cells to define phenotypic effects on cellular function. We have identified mutations in G proteins and in G protein- coupled receptors as the basis of several human diseases. 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.