Biology Reference
In-Depth Information
PKA
or CamKII
CaM
CaM
PDE1 (3)
PDE1 (3)
P
cG
PDE2 (1)
PDE2 (1)
A
B
PKB PKB
PKA
PKA
TM
PDE3 (2)
PDE3 (2)
P
P
P
P
ERK2
PKA
PDE4 (4)
PDE4 (4)
P
P
1
2
cG
PKG
PDE5 (1)
PDE5 (1)
P
A
B
cG
p
g
PDE6 (3)
PDE6 (3)
A
B
PDE7 (2)
PDE7 (2)
PDE8 (2)
PDE8 (2)
PDE9 (1)
PDE9 (1)
cA
PKA
PDE10 (1)
PDE10 (1)
P
A
B
cG
PDE11 (1)
PDE11 (1)
A
B
CaM binding
GAF domain
PAS domain
UCR
Anchoring
Fig. 1 Schematic representation of domain arrangment of the 11 mammalian PDE families.
Family name is noted to the
right
of each structure, and the
number in parenthesis
denotes the
number of genes composing the family. The conserved catalytic domain is represented as a
red
cylinder
. Binding proteins are depicted in
yellow
.TM
ΒΌ
transmembrane domain of PDE3; protein
kinase (PKB, PKA, PKG, ERK, or CaMKII) phosphorylation sites are shown as a
teal ball
labeled
with a P. Cyclic GMP binding to either GAF-A or GAF-B domains is marked by a
red ball
labeled
cG, and cAMP binding to GAF-B in PDE10 is depicted as a
pink ball
labeled cA. Modified from
Conti and Beavo (
2007
)
a cell. Some PDE families (PDEs 1-4) are widely expressed in mammalian tissues,
but others (PDEs 5-11) occur in lower abundance or are expressed in fewer tissues.
The PDE6 family appears to be the most restricted in distribution since it has only
been found in the outer segments of photoreceptors, where it is in high concentration,
and in the pineal gland (Cote
2006
).
1.1 PDEs as Cellular Targets of Cyclic Nucleotides
The myriad forms of PDEs that serve as cellular targets of cNs and as major deter-
minants of cN action exceed those of other targets such as that of cN-dependent
