Molecular Biology of the Cell by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morgan, Martin Raff, Keith Roberts, Peter Walter by by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morg

886 Chapter 15: Cell Signaling
Problems
Which statements are true? Explain why or why not.
15–1 All second messengers are water-soluble and diffuse
freely through the cytosol.
15–2 In the regulation of molecular switches, protein
kinases and guanine nucleotide exchange factors (GEFs)
always turn proteins on, whereas protein phosphatases
and GTPase-activating proteins (GAPs) always turn proteins
off.
15–3 Most intracellular signaling pathways provide
numerous opportunities for amplifying the responses to
extracellular signals.
15–4 Binding of extracellular ligands to receptor tyrosine
kinases (RTKs) activates the intracellular catalytic
domain by propagating a conformational change across
the lipid bilayer through a single transmembrane α helix.
15–5 Protein tyrosine phosphatases display exquisite
specificity for their substrates, unlike most serine/threonine
protein phosphatases, which have rather broad
specificity.
15–6 Even though plants and animals independently
evolved multicellularity, they use virtually all the same signaling
proteins and second messengers for cell–cell communication.
Discuss the following problems.
15–7 Suppose that the circulating concentration of hormone
is 10 –10 M and the K d for binding to its receptor is 10 –8
M. What fraction of the receptors will have hormone bound?
If a meaningful physiological response occurs when 50% of
the receptors have bound a hormone molecule, how much
will the concentration of hormone have to rise to elicit a
response? The fraction of receptors (R) bound to hormone
(H) to form a receptor–hormone complex (R–H) is [R–H]/
([R] + [R–H]) = [R–H]/[R] TOT = [H]/([H] + K d ).
15–8 Cells communicate in ways that resemble human
communication. Decide which of the following forms of
human communication are analogous to autocrine, paracrine,
endocrine, and synaptic signaling by cells.
A. A telephone conversation
B. Talking to people at a cocktail party
C. A radio announcement
D. Talking to yourself
15–9 Why do signaling responses that involve changes
in proteins already present in the cell occur in milliseconds
to seconds, whereas responses that require changes
in gene expression require minutes to hours?
15–10 How is it that different cells can respond in different
ways to exactly the same signaling molecule even when
they have identical receptors?
15–11 Why do you suppose that phosphorylation/
dephosphorylation, as opposed to allosteric binding of
small molecules, for example, has evolved to play such a
prominent role in switching proteins on and off in signaling
pathways?
15–12 Consider a signaling pathway that proceeds
through three protein kinases that are sequentially activated
by phosphorylation. In one case, the kinases are
held in a signaling complex by a scaffolding protein; in
the other, the kinases are freely diffusible (Figure Q15–1).
Discuss the properties of these two types of organization
in terms of signal amplification, speed, and potential for
cross-talk between signaling pathways.
2
3
1
15–13 Describe three ways in which a gradual increase in
an extracellular signal can be sharpened by the target cell
to produce an abrupt or nearly all-or-none response.
15–14 Problems Activation p15.02/15.01
(“maturation”) of frog oocytes is signaled
through a MAP kinase signaling module. An increase
in the hormone progesterone triggers the module by stimulating
the translation of Mos mRNA, which is the frog’s
MAP kinase kinase kinase (Figure Q15–2). Maturation is
easy to score visually by the presence of a white spot in
the middle of the brown surface of the oocyte (see Figure
Q15–2). To determine the dose–response curve for progesterone-induced
activation of MAP kinase, you place 16
oocytes in each of six plastic dishes and add various concentrations
of progesterone. After an overnight incubation,
you crush the oocytes, prepare an extract, and determine
the state of MAP kinase phosphorylation (hence, activation)
by SDS polyacrylamide-gel electrophoresis (Figure
Q15–3A). This analysis shows a graded response of MAP
kinase to increasing concentrations of progesterone.
1 mm
CYTOSOL
progesterone
Mos
MEK1
MAPK
1
3
2
Figure Q15–2 Progesterone-induced
MAP kinase activation, leading to oocyte
maturation (Problem 15–14). (Courtesy
of Helfrid Hochegger.)
mature oocytes
Figure Q15–1 A kinase
cascade organized by
a scaffolding protein
or composed of freely
diffusing components
(Problem 15–12).