Essential Cell Biology 5th edition

A:42 Answers
3. The response to a signal would be much less rapid,
because the signal-dependent increase in GTP-bound
Ras would occur over an elevated background of
preexisting GTP-bound Ras.
4. The increase in Ras activity in response to a signal would
also be prolonged compared to the response in normal
cells.
(A)
K K K K K K K K
kinase
domain
P P
K
K
ANSWER 16–10
A. Both types of signaling can occur over a long range:
neurons can send action potentials along very long
axons (think of the axons in the neck of a giraffe, for
example), and hormones are carried via the bloodstream
throughout the organism. Because neurons secrete large
amounts of neurotransmitters at a synapse, a small, welldefined
space between two cells, the concentrations
of these signal molecules are high; neurotransmitter
receptors, therefore, need to bind to neurotransmitters
with only low affinity. Hormones, in contrast, are vastly
diluted in the bloodstream, where they circulate at often
minuscule concentrations; hormone receptors therefore
generally bind their hormone with extremely high
affinity.
B. Whereas neuronal signaling is a private affair, with one
neuron talking to a select group of target cells through
specific synaptic connections, endocrine signaling
is a public announcement, with any target cell with
appropriate receptors able to respond to the hormone in
the blood. Neuronal signaling is very fast, limited only by
the speed of propagation of the action potential and the
workings of the synapse, whereas endocrine signaling is
slower, limited by blood flow and diffusion over larger
distances.
ANSWER 16–11
A. There are 100,000 molecules of X and 10,000 molecules
of Y in the cell (= rate of synthesis × average lifetime).
B. After one second, the concentration of X will
have increased by 10,000 molecules per cell. The
concentration of X, therefore, one second after its
synthesis is increased, is about 110,000 molecules per
cell—which is a 10% increase over the concentration of
X before the boost of its synthesis. The concentration
of Y will also increase by 10,000 molecules per cell,
which, in contrast to X, represents a full twofold increase
in its concentration (for simplicity, we can neglect the
breakdown in this estimation because X and Y are
relatively stable during the one-second stimulation).
C. Because of its larger proportional increase, Y is the
preferred signaling molecule. This calculation illustrates
the surprising but important principle that the time it
takes to switch a signal on is determined by the lifetime
of the signaling molecule.
ANSWER 16–12
A. The mutant RTK lacking its extracellular ligand-binding
domain is inactive. It cannot bind extracellular signals,
and its presence has no consequences for the function
of the normal RTK (Figure A16–12A). If the mutant
receptors are present at extremely high levels, however,
they might dimerize in the absence of the extracellular
signal molecule, causing activation of signaling.
B. The mutant RTK lacking its intracellular domain is also
inactive, but its presence will block signaling by the
normal receptors. When a signal molecule binds to
(B)
K
K
Figure A16–12
either receptor, ECB5 EA16.06/A16.13
it will induce their dimerization. Two
normal receptors have to come together to activate
each other by phosphorylation. In the presence of an
excess of mutant receptors, however, normal receptors
will usually form mixed dimers, in which their intracellular
domain cannot be activated because their partner is a
mutant and lacks a kinase domain (Figure A16–12B).
ANSWER 16–13 The statement is largely correct. Upon
ligand binding, transmembrane helices of multispanning
receptors, like the GPCRs, shift and rearrange with respect
to one another (Figure A16–13A). This conformational
change is sensed on the cytosolic side of the membrane
because of a change in the arrangement of the cytoplasmic
loops. A single transmembrane segment is not sufficient
to transmit a signal across the membrane directly; no
rearrangements in the membrane are possible upon ligand
binding. Thus, upon ligand binding, single-span receptors
such as most RTKs tend to dimerize, thereby bringing their
intracellular kinase domains into proximity so that
they can cross-phosphorylate and activate each other
(Figure A16–13B).
(A)
(B)
transmembrane
helices of
receptor proteins
Figure A16–13
extracellular
signal molecule
extracellular
signal molecule
K
CYTOSOL
activated enzyme
domain of receptors
K