Essential Cell Biology 5th edition

G-Protein-Coupled Receptors
551
epinephrine
plasma
membrane
activated GPCR
(adrenergic receptor)
activated
adenylyl cyclase
inactive PKA
cAMP
GTP
activated α subunit of
stimulatory G protein (G s )
ATP
cyclic AMP
CYTOSOL
Figure 16–21 Epinephrine stimulates
glycogen breakdown in skeletal muscle
cells. The hormone activates a GPCR, which
turns on a G protein (G s ) that activates
adenylyl cyclase to boost the production
of cyclic AMP. The increase in cyclic AMP
activates PKA, which phosphorylates and
activates an enzyme called phosphorylase
kinase. This kinase activates glycogen
phosphorylase, the enzyme that breaks
down glycogen (see Figure 13–22). Because
these reactions do not involve changes in
gene transcription or new protein synthesis,
they occur rapidly.
active PKA
inactive
phosphorylase
kinase
ATP
ADP
P
ATP
ADP
active
phosphorylase
kinase
P
active glycogen
phosphorylase
inactive
glycogen
phosphorylase
GLYCOGEN
BREAKDOWN
sudden action. In skeletal muscle, for instance, epinephrine increases
intracellular cyclic AMP, causing the breakdown of glycogen—the polymerized
storage form of glucose. It does so by activating PKA, which leads
to both the activation of an enzyme that promotes glycogen breakdown
(Figure 16–21) and the inhibition of an enzyme that drives glycogen synthesis.
By stimulating glycogen breakdown and inhibiting its synthesis,
ECB5 e16.25/16.21
the increase in cyclic AMP maximizes the amount of glucose available as
fuel for anticipated muscular activity. Epinephrine also acts on fat cells,
stimulating the breakdown of fat to fatty acids. These fatty acids can then
be exported to fuel ATP production in other cells.
In some cases, the effects of increasing cyclic AMP are rapid; in skeletal
muscle, for example, glycogen breakdown occurs within seconds of epinephrine
binding to its receptor (see Figure 16–21). In other cases, cyclic
AMP responses involve changes in gene expression that take minutes
or hours to develop. In these slow responses, PKA typically phosphorylates
transcription regulators, proteins that activate the transcription
of selected genes (as discussed in Chapter 8). For example, an increase
in cyclic AMP in certain neurons in the brain controls the production of
proteins involved in some forms of learning. Figure 16–22 illustrates a
typical cyclic-AMP-mediated pathway from the plasma membrane to the
nucleus.
We now turn to the other enzyme-mediated signaling pathway that leads
from GPCRs—the pathway that begins with the activation of the membrane-bound
enzyme phospholipase C and leads to an increase in the
second messengers diacylglycerol, inositol trisphosphate, and Ca 2+ .
QUESTION 16–4
Explain why cyclic AMP must be
broken down rapidly in a cell to
allow rapid signaling.