Essential Cell Biology 5th edition

552 CHAPTER 16 Cell Signaling
Figure 16–22 A rise in intracellular cyclic
AMP can activate gene transcription.
PKA, activated by a rise in intracellular
cyclic AMP, can enter the nucleus and
phosphorylate specific transcription
regulators. Once phosphorylated, these
proteins stimulate the transcription of a
whole set of target genes (Movie 16.3).
This type of signaling pathway controls
many processes in cells, ranging from
hormone synthesis in endocrine cells to the
production of proteins involved in long-term
memory in the brain. Activated PKA can also
phosphorylate and thereby regulate other
proteins and enzymes in the cytosol, as
shown in Figure 16–21.
inactive PKA
CYTOSOL
NUCLEUS
cyclic AMP
nuclear pore
activated, phosphorylated
transcription regulator
P
active
PKA
active
PKA
inactive
transcription
regulator
activated target gene
TRANSCRIPTION OF
TARGET GENE
The Inositol Phospholipid Pathway Triggers a Rise in
Intracellular Ca 2+
Some GPCRs exert their effects through a G protein called G q , which activates
the membrane-bound enzyme phospholipase C instead of adenylyl
cyclase. Examples of signal molecules that act through phospholipase C
are given in Table 16−4.
Once activated, phospholipase C propagates the signal by cleaving a lipid
molecule that is a component of the plasma membrane. The molecule is
an inositol phospholipid (a phospholipid with the sugar inositol attached
to its head) that is present ECB5 in small e16.26/15.22 quantities in the cytosolic leaflet of the
membrane lipid bilayer (see Figure 11–19). Because of the involvement
of this phospholipid, the signaling pathway that begins with the activation
of phospholipase C is often referred to as the inositol phospholipid
pathway. It operates in almost all eukaryotic cells and regulates a large
number of different effector proteins.
The cleavage of a membrane inositol phospholipid by phospholipase C
generates two second messenger molecules: inositol 1,4,5-trisphosphate
(IP 3 ) and diacylglycerol (DAG). Both molecules play a crucial part
in relaying the signal (Figure 16–23).
IP 3 is a water-soluble sugar phosphate that is released into the cytosol;
there it binds to and opens Ca 2+ channels that are embedded in the endoplasmic
reticulum (ER) membrane. Ca 2+ stored inside the ER rushes out
TABLE 16–4 SOME CELL RESPONSES MEDIATED BY PHOSPHOLIPASE C
ACTIVATION
Signal Molecule Target Tissue Major Response
Vasopressin (a peptide hormone) liver glycogen breakdown
Acetylcholine pancreas secretion of amylase
(a digestive enzyme)
Acetylcholine skeletal muscle contraction
Thrombin (a proteolytic enzyme) blood platelets aggregation