Cell Junctions, Structure, Function, and Regulation
341
and
β
3
integrins in cholesterol-rich mem-
brane domains. CD47-integrin association
enhances the interaction of integrins with
their ligands, as well as integrin function in
adhesion and migration. The mechanisms
involve signaling through heterotrimeric
Gi
α
proteins.
1.4
Focal Adhesions
1.4.1
Components of Focal Adhesion
One of the most studied cell–matrix junc-
tions is the focal adhesion, sometimes
referred to as the focal contact. Focal ad-
hesions contain clustered integrins that
mediate very tight adhesion with their
ECM ligands and also associate with the
ends of actin stress ±bers. More than
50 proteins have been shown to local-
ize to focal adhesions. Not surprisingly,
many of the proteins that can bind to
integrin-
β
cytoplasmic domains, as well as
proteins that function in integrin signaling
pathways are concentrated in focal adhe-
sions (Figs. 3 and 6). As discussed above,
several of these proteins are tyrosine-
phosphorylated; thus, focal adhesions can
be visualized by using antibodies that rec-
ognize phosphotryrosine residues (Fig. 7).
In general, focal adhesion proteins con-
tain multiple protein–protein interaction
domains enabling them to bind to several
proteins simultaneously. Indeed, many
focal adhesion proteins function in mul-
tiprotein complexes linking integrins, the
actin cytoskeleton and multiple signaling
cascades. For example, FAK binds to pax-
illin, talin, p130Cas, Src family kinases, PI
3-kinase, Grb2, and Grb7. Paxillin bind-
ing partners include vinculin, FAK, ILK,
the tyrosine phosphatase PTP-PEST, PKL,
and CrkII. Long lists of binding partners
canbemadeformostfoca
ladhes
ionpro
-
teins. On the basis of biochemical studies
that have characterized protein–protein
PM
Fibronectin
Talin
Vin
Src
FAK
p130Cas
Talin
Vin
FAK
Paxillin
PI 3-K
PKL
PIX
Crk
Dock180
ILK
Paxillin
Pinch
a
-actinin
Tensin
Filamin
Migfilin
Actin stress fibers
ABL
PTP-PEST
PAK
aa
a
a
a
bb
b
b b
Fig. 6
Components of focal adhesions. Shown is a schematic of a focal adhesion. Only a
subset of proteins and protein interactions present at focal adhesion is shown. Vinculin is
abbreviated as vin.
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