Cell Junctions, Structure, Function, and Regulation
339
b
1
b
2
b
3
b
5
b
6
b
7
b
8
b
4
PM
Cytoplasmic domains
FN-1
FN-2
FN-3
FN-4
CS
KLL
MI
IHDRREFAKFEKE
KMN
AKW
D
T
GE
NP
I
YKSA
VTTVV
NP
K
Y
EGK
K
A
L
IHLS
D
L
RE
YRR
FEKE
KLKSQ
W
NND
NPL
F
KSA
TTTVM
NP
K
F
AES
KLL
IT
IHDR
K
EFAKFE
E
E
RAR
AKW
D
T
AN
NPLYK
EATSTF
N
IT
Y
RGT
KLLV
T
IHDRREFAK
QSERSRARYEMAS
NPLY
RKPISTHTVDFTFNKF
N
KS
Y
NGTVD
KLLV
SF
HDR
K
E
V
AKFE
A
E
RSK
AKW
Q
T
GT
NPLY
RGSTSTFK
N
VT
Y
KHREKQKVDLSTDC
R
L
S
V
E
I
Y
DRRE
YSR
FEKE
QQQLN
W
KQDS
NPLYKSA
ITTTI
NP
R
F
QEADSPTL
RQVILQWNSNKIKSSSDYRVSASKKDKLILQSVCTRAVTYRREKPEEIKMDISKLNAHETFRCNF
Fig. 5
Comparison of integrin
β
-subunit cytoplasmic domains. The amino acid sequences
of the
β
1
–
β
8
cytoplasmic domains are shown, with the exception of
β
4
.Aminoac
idsthatare
conserved in at least three
β
-cytoplasmic domains are shown in red. The
β
2
and
β
7
cytoplasmic domains contain NPXF motifs in place of NPXY motifs found in other
β
-cytoplasmic domains. These phenylalanine residues (F) are shown in green. The
conservedNPXY/Fmotifsareind
icatedbydashedboxes.The
β
4
cytoplasmic domain
contains 1000 amino acids with 4 regions homologous to conserved domains identi±ed ±rst
in ±bronectin, referred to as ±bronectin type III repeats. These regions are labeled FN-1 to
FN-4 in the
β
4
cytoplasmic domain. The ±rst pair of FN repeats is separated by a region
referred to as the connecting segment (CS) (see color plate p. xxiii).
of FAK by integrins. Interestingly, phos-
phorylated FAK has been shown to bind
to the C-terminal region of the
β
5
tail.
This interaction is important for vascu-
lar endothelial growth factor (VEGF) to
promote migration mediated by the
α
v
β
5
integrin. Integrin-linked kinase (ILK) has
also been shown to bind to the
β
1
and
β
3
tails. In addition to its serine/threonine
kinase activity, ILK also functions as an
adaptor protein that localizes to focal ad-
hesions. ILK plays a role in the regulation
of cell adhesion, cell proliferation and ±-
bronectin matrix assembly; however, there
is no evidence that ILK-
β
tail interactions
are required for ILK function in these
processes.
β
tail–speci±c
protein
interactions
have been identi±ed for the
β
1
,β
2
,β
3
,
and
β
5
cytoplasmic domains. Many of
these interactions regulate integrin-ligand
interactions.
Cytohesins
bind
speci±-
cally to the
β
2
cytoplasmic domain to
upregulate
β
2
integrin-dependent adhe-
sion.
β
3
-endonexin binds speci±cally to
the
β
3
tail and increases the ability of
α
IIb
β
3
to bind to its ligand. Although talin
is not a
β
-tail-speci±c binding protein,
it is interesting to note that the binding
of a fragment of talin to the
β
3
tail can
also activate
α
IIb
β
3
.Thu
s
,
β
3
-endonexin
and talin may both regulate the activa-
tion of
α
IIb
β
3
. TAP-20 binds speci±cally
to the
β
5
tail and appears to play a role
in promoting
α
v
β
5
-dependent migration
by decreasing
α
v
β
5
-mediated adhesion.
Interestingly, TAP-20 shares amino acid
homology with
β
3
-endonexin, although
their functions may be distinct since
β
3
-
endonexin enhances
α
IIb
β
3
-ligand interac-
tions. Integrin-associated protein-1 (ICAP-
1) binds speci±cally to the
β
1
cytoplasmic
