Essential Cell Biology 5th edition

550 CHAPTER 16 Cell Signaling
Figure 16–20 The concentration of
cyclic AMP rises rapidly in response to
an extracellular signal. A nerve cell in
culture responds to the binding of the
neurotransmitter serotonin to a GPCR by
synthesizing cyclic AMP. The concentration
of intracellular cyclic AMP was monitored
by injecting into the cell a fluorescent
protein whose fluorescence changes when
it binds cyclic AMP. Blue indicates a low
level of cyclic AMP, yellow an intermediate
level, and red a high level. (A) In the resting
cell, the cyclic AMP concentration is about
5 × 10 –8 M. (B) Fifty seconds after adding
serotonin to the culture medium, the
intracellular concentration of cyclic AMP
has risen more than twentyfold (to >10 –6 M)
in the parts of the cell where the serotonin
receptors are concentrated. (From B.J.
Bacskai et al. Science 260:222–226, 1993.)
(A)
time 0 sec
+ serotonin
Cyclic AMP phosphodiesterase is continuously active inside the cell.
Because it eliminates cyclic AMP so quickly, the cytosolic concentration
of this second messenger can change rapidly in response to extracellular
signals, rising or falling tenfold in a matter of seconds (Figure 16–20).
Cyclic AMP is water-soluble, so it can, in some cases, carry the signal
throughout the cell, traveling from the site on the membrane where
it is synthesized to interact with proteins located in the cytosol, in the
nucleus, or on other organelles.
Cyclic AMP exerts most of its effects by activating the enzyme cyclic-
AMP-dependent protein kinase ECB5 e16.24/16.20
(PKA). This enzyme is normally held
inactive in a complex with a regulatory protein. The binding of cyclic AMP
to the regulatory protein forces a conformational change that releases
the inhibition and unleashes the active kinase. Activated PKA then catalyzes
the phosphorylation of particular serines or threonines on specific
intracellular proteins, thus altering the activity of these target proteins. In
different cell types, different sets of proteins are available to be phosphorylated,
which largely explains why the effects of cyclic AMP vary with the
type of target cell.
Many kinds of cell responses are mediated by cyclic AMP; a few are listed
in Table 16−3. As the table shows, different target cells respond very
differently to extracellular signals that change intracellular cyclic AMP
concentrations. When we are frightened or excited, for example, the
adrenal gland releases the hormone epinephrine (also called adrenaline),
which circulates in the bloodstream and binds to a class of GPCRs called
adrenergic receptors (see Figure 16–14B), which are present on many
types of cells. The consequences of epinephrine binding vary from one
cell type to another, but all the cell responses help prepare the body for
(B)
time 50 sec
TABLE 16–3 SOME CELL RESPONSES MEDIATED BY CYCLIC AMP
Extracellular Signal
Molecule*
Target Tissue
Major Response
Epinephrine heart increase in heart rate and force of
contraction
Epinephrine skeletal muscle glycogen breakdown
Epinephrine,
glucagon
Adrenocorticotropic
hormone (ACTH)
fat
adrenal gland
fat breakdown
cortisol secretion
*Although all of the signal molecules listed here are hormones, some responses
to local mediators and to neurotransmitters are also mediated by cyclic AMP.