Essential Cell Biology 5th edition

562 CHAPTER 16 Cell Signaling
growth factor
P
P
activated RTK
plasma
membrane
Figure 16–34 Akt stimulates cells to grow in size by activating
the serine/threonine kinase Tor. The binding of a growth factor to
an RTK activates the PI-3-kinase–Akt signaling pathway (as shown in
Figure 16−32). Akt then indirectly activates Tor by phosphorylating
and inhibiting a protein that helps to keep Tor shut down (not shown).
Tor stimulates protein synthesis and inhibits protein degradation by
phosphorylating key proteins in these processes (not shown). The
anticancer drug rapamycin slows cell growth by inhibiting Tor. In fact,
the Tor protein derives its name from the fact that it is a target of
rapamycin.
activated PI 3-kinase
inhibition of
protein
degradation
activated Akt
activated Tor
stimulation
of protein
synthesis
CELL GROWTH
ECB5 e16.39/16.34
a large serine/threonine kinase called Tor. Tor stimulates cells to grow
both by enhancing protein synthesis and by inhibiting protein degradation
(Figure 16–34). The anticancer drug rapamycin works by inactivating
Tor, indicating the importance of this signaling pathway in regulating
cell growth and survival—and the consequences of its disregulation in
cancer.
The main intracellular signaling cascades activated by GPCRs and RTKs
are summarized in Figure 16–35. As dauntingly complex as such pathways
may seem, the complexity of cell signaling is actually much greater
still. First, we have not discussed all of the intracellular signaling pathways
that operate in cells. Second, although we depict these signaling
pathways as being relatively linear and self-contained, they do not
operate entirely independently. We will return to this concept of signal
integration at the chapter’s conclusion. But first, we take a brief detour to
introduce a few important types of signaling systems that we have thus
far overlooked.
signal molecule
signal molecule
plasma membrane
activated GPCR
P
P
activated RTK
G protein
G protein
phospholipase C
PI 3-kinase
Figure 16–35 Both GPCRs and
RTKs activate multiple intracellular
signaling pathways. The figure
reviews five of these pathways:
two leading from GPCRs—through
adenylyl cyclase and through
phospholipase C—and three leading
from RTKs—through phospholipase C,
Ras, and PI 3-kinase. Each pathway
differs from the others, yet they
use some common components to
transmit their signals. Because all five
eventually activate protein kinases
(gray boxes), it seems that each is
capable in principle of regulating
practically any process in the cell.
adenylyl cyclase
IP 3
Ca 2+
cyclic AMP
calmodulin
PKA
CaM-kinase
transcription regulators
diacylglycerol
PKC
Ras-GEF
Ras
MAP kinase kinase kinase
protein kinase 1
MAP kinase kinase
MAP kinase
many target proteins
phosphorylated
inositol
phospholipid
Akt kinase