BIO254:Gprotein: Difference between revisions

The role of cAMP-dependent signal transduction was known in the 1950s and 1960s; however, the essential role of GTP was masked by the fact that cAMP preparations were contaminated by GTP (Milligan, 2006).  In the 1970s a mutated cell line was found to have an intact ligand receptor and amplifier, yet this cell line did not respond to the receptors ligand (Fig. 3), implying the existence of an intermediary and also providing a cell line on which reconstitution assays could be performed.  Alfred G. Gilman purified and identified this intermediary in 1980 (Northup, 1980) by reconstituting the complete pathway by adding a purified protein, the G-protein.  [[Image: NobelA.jpg|frame|center|Figure 3a. Image modified from http://nobelprize.org/nobel_prizes/medicine/laureates/1994/illpres/disc-gprot.html.]][[Image: NobelB.jpg|frame|center|Figure 3b. Image modified from http://nobelprize.org/nobel_prizes/medicine/laureates/1994/illpres/disc-gprot.html.]]

The heterotrimeric G protein that Gilman isolated increased cAMP levels.  In 1980 Martin Rodbell wrote a review (Rodbell, 1980) that helped direct the search for the first cAMP reducing G-protein to be discovered, in 1984.  Martin Rodbell and Alfred G. Gilman were awarded the 1994 Nobel Prize in Physiology and Medicine for the discovery of "G-proteins and the role of these proteins in signal transduction in cells".  Since the first G-proteins were identified, many others with effectors other than cAMP have been cloned, in many cases by homology.  Currently 16 alpha, 5 beta, and 14 gamma subunits have been identified (Milligan, 2006).