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Alfred G. Gilman,
Martin Rodbell (1994)
"for the discovery of G-proteins and the role of these
proteins in signal transduction in cells"
Martin Rodbell showed in 1971 that the transduction
of a message from the exterior of the cell to its interior
requires the cooperation of three functional units:
1) a discriminator (receptor) that recognizes different
extracellular signals (first messengers), 2) a transducer
that requires GTP, and 3) an amplifier that generates
large quantities of a second messenger.
Alfred Gilman and his coworkers used leukemia cells to
identify and demonstrate G-proteins. Normal leukemia
cells respond with a normal biological response to the
appropriate first messenger. In mutated cells, however, no
response was evoked, because the cells lacked the
G-protein. The function could be restored by G-protein
derived from another tissue such as brain.
Robert J. Lefkowitz,
Brian K. Kobilka (2012)
"for studies of G-protein-coupled receptors"
Cartoon of a cell with its interior (light blue) and exterior (blue),
with their different chemical compositions separated by a
phospholipid bilayer. The bilayer contains many proteins. Shown
are two copies of a GPCR with specificity for a diffusible ligand
(yellow). The fraction of receptors with bound ligand is governed
by the ligand concentration. The receptor to the left is unoccupied
and non-activated, and the receptor to the right is occupied by a
ligand, bound to a G-protein (red), and activated. The ligand does
not pass through the membrane; the signal is transmitted by
conformational changes in the receptor protein.
The prediction of seven helices in βAR
is shown above rhodopsin. The
homologous amino acid sequences in
helices five, six and seven are aligned,
and identities and similarities are