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

836 Chapter 15: Cell Signaling
signal molecule
activated GPCR
activated
adenylyl cyclase
cyclic AMP
activated α
subunit of
stimulatory G
protein (G s )
GTP
ATP
plasma
membrane
CYTOSOL
Figure 15–27 How a rise in intracellular
cyclic AMP concentration can alter
gene transcription. The binding of an
extracellular signal molecule to its GPCR
activates adenylyl cyclase via G s and
thereby increases cAMP concentration in
the cytosol. This rise activates PKA, and
the released catalytic subunits of PKA
can then enter the nucleus, where they
phosphorylate the transcription regulatory
protein CREB. Once phosphorylated,
CREB recruits the coactivator CBP, which
stimulates gene transcription. In some
cases, at least, the inactive CREB protein is
bound to the cyclic AMP response element
(CRE) in DNA before it is phosphorylated
(not shown). See Movie 15.2.
inactive PKA
activated
PKA
CYTOSOL
NUCLEUS
nuclear pore
activated PKA
activated, phosphorylated CREB
CREB-binding
protein (CBP)
P
inactive CREB
activated target gene
cyclic AMP response
element (CRE)
GENE TRANSCRIPTION
for example, cAMP activates the gene that encodes this hormone. The regulatory
region of the somatostatin gene contains a short cis-regulatory sequence, called
the cyclic AMP response element (CRE), which is also found in the regulatory
region of many other genes activated by cAMP. A specific transcription regulator
called CRE-binding (CREB) protein recognizes this sequence. When PKA is activated
by cAMP, it phosphorylates CREB on a single serine; phosphorylated CREB
MBoC6 m15.36/15.27
then recruits a transcriptional coactivator called CREB-binding protein (CBP),
which stimulates the transcription of the target genes (Figure 15–27). Thus, CREB
can transform a short cAMP signal into a long-term change in a cell, a process
that, in the brain, is thought to play an important part in some forms of learning
and memory.
Some G Proteins Signal Via Phospholipids
Many GPCRs exert their effects through G proteins that activate the plasma-membrane-bound
enzyme phospholipase C-β (PLCβ). Table 15–2 lists some examples
of responses activated in this way. The phospholipase acts on a phosphorylated
inositol phospholipid (a phosphoinositide) called phosphatidylinositol
4,5-bisphosphate [PI(4,5)P 2 ], which is present in small amounts in the inner half
of the plasma membrane lipid bilayer (Figure 15–28). Receptors that activate this
inositol phospholipid signaling pathway mainly do so via a G protein called G q ,
which activates phospholipase C-β in much the same way that G s activates adenylyl
cyclase. The activated phospholipase then cleaves the PI(4,5)P 2 to generate two