334
Cell Junctions, Structure, Function, and Regulation
RAC
DOCK180
CRK11
p130CAS
ARP2/3
NWASP
Cdc42
mDIA
ROCK
Rho
CRKII
p130CAS
DOCK180
RAC
Cell survival
Cell proliferation
Cell motility
PM
Fibronectin
FAK, Src, ILK
FAK, Src, ILK
Paxillin,
a
-actinin,
talin, filamin
FAK, Src, ILK
JNK
AKT
PI 3-K
NFKB
Plus growth factors and cytokines
ERK MAPK
RAS
CYCLIN D1
ERK MAPK
RAS
CYCLIN D1
FAK, Src, ILK
a
-actinin, paxillin,
talin, filamin
Cytoskeletal
organization
ab
ab
ab
ab
ab
Fig. 3
Integrin signaling. Pathways regulated by
integrin signaling that promote cell motility,
proliferation, and survival are shown in the
diagram. Integrins signal together with growth
factor and cytokine receptors to regulate cell
motility, survival, and proliferation, although the
mechanisms of cooperation between these
different types of cell surface receptors are not
fully deFned. Most of the cytoskeletal, adaptor
and signaling proteins are described in the text.
In addition to these are the N±KB transcription
factor, the kinase ROCK, which is activated by
Rho and in turn activates actinomyosin
contractility, and mDIA, which is also activated
byRhotopromoteactinpo
lymerization.A
lso
shown is Cdc42, which activates NWASP, which
in turn activates the Arp2/3 complex to nucleate
actin polymerization.
that trigger many downstream signals. The
small GTP-binding protein Ras gets ac-
tivated downstream of FAK/Src kinases
and, in turn, Ras triggers the activation of
ERK MAP kinase and PI 3-kinase. How-
ever, FAK can also activate PI 3-kinase
directly. In turn, PI 3-kinase plays a role
in the activation of several other signaling
proteins. It generates PIP3 phospholipids,
which provide bindings sites at the plasma
membrane for PH domains, which are
conserved domains present on many dif-
ferent types of signaling proteins. PI
3-kinase signaling plays a role in activating
the kinase AKT and the Rho family of GTP-
binding proteins, Cdc42, Rac and Rho.
AKT signaling promotes cell survival and
proliferation, whereas the Rho family GT-
Pases regulate the actin cytoskeleton. The
Rho family is particularly important in
adhesion signaling. Cdc42 and Rac pro-
mote actin polymerization, resulting in
the formation of ±lopodia and lamellipo-
dia, respectively. The formation of these
structures drives cell spreading and mi-
gration. Rho promotes the formation of
previous page 1008 Encyclopedia of Molecular Cell Biology and Molecular Medicine read online next page 1010 Encyclopedia of Molecular Cell Biology and Molecular Medicine read online Home Toggle text on/off