Cellular Interactions
467
KII is dependent on the presence of both
calmodulin and calcium. While functions
of CaM KII have been demonstrated in
eggs from other classes of organisms,
there are not many reports concerning
CaM KII activation in mammalian eggs.
Several roles for CaM KII are summarized
in Fig. 1. There is general agreement from
many sources that the rise in intracellular-
free calcium inactivates maturation pro-
motion factor (MPF) by targeting cyclin
B1 for degradation through an ubiquitin-
dependent pathway. In addition, Protein
kinase C (PKC) acts downstream of the
calcium signal and there have been sev-
eral reports demonstrating this activation
at a biochemical or immunocytochemi-
cal level in mouse and rat eggs, although
the speci±c isotypes of PKC that act ap-
pear to differ depending on the study and
species. Once activated, PKC appears to
have several roles as summarized in Fig. 1
including the release of PKC’s catalytic
domain (i.e. PKM). Until recently MAP
kinase (mitogen-activated protein kinase)
was thought to function independent of
the other three pathways in Fig. 1.
1.2
Signals Regulated by Kinases
In the mammalian egg, there are three
well-studied kinases that are regulated by
calcium. Protein kinase C and calcium/cal-
modulin-dependent
protein
kinase
II
(CaM KII) are activated by calcium, while
MPF is inactivated by calcium.
There are at least 12 different isotypes
of PKC that range in molecular weight
from about 67 to 76 kDa and all phos-
phorylate serine and threonine residues in
protein. The isotypes are organized into
three groups referred to as conventional,
atypical, and novel by the cofactors re-
quired to activate the different isotypes.
The conventional PKC isotypes,
α
,
β
I,
β
II, and
γ
, are activated by diacylglycerol
(DAG) and negatively charged phospho-
lipids in a calcium-dependent manner. The
atypical PKC isotypes
ζ
and
λ
require neg-
atively charged phospholipids but do not
require DAG or calcium. The novel PKC
isotypes
δ
,
ε
,
θ
,
η
,and
µ
do not require cal-
cium but require DAG and phospholipids
as cofactors. Some investigators regard
PKC
µ
isotype as a different category
of kinase because it has a unique struc-
ture. Conventional isotypes are the most
likely to act proximally downstream of the
calcium signal induced by fertilization of
mammalian eggs because they require cal-
cium as a cofactor. It has been shown that
cells can contain more than one isotype of
PKC and thus, depending on the cofactors
generated, members of this kinase family
have the potential to influence a variety of
different pathways in a single cell as well as
have different effects in different cells. The
different isotypes can have different sub-
strate speci±city allowing one PKC isotype
to have different effects on the cell rather
than activation of another isotype in the
same cell. Work with somatic cells has sug-
gested that at least one of these isotypes,
PKC
λ
,m
a
ys
e
r
v
et
od
e
c
o
d
eb
o
thc
a
l
-
cium oscillations and DAG signals. These
features are most likely important to mam-
malian eggs because not only has PKC
λ
been identi±ed in mouse eggs but at least
seven different isotypes of PKC have also
been recently identi±ed at the protein level
in both mouse eggs and early embryos.
There are several isotypes of calcium/cal-
modulin-dependent protein kinase II
α
,
β
,
γ
,
δ
and, the functional enzyme is a het-
eromultimer composed of several catalytic
subunits, but for the kinase to be active not
all subunits are required. CaM KII is a large
kinase with a molecular weight of 50 kDa
and requires an association with calcium
previous page 1141 Encyclopedia of Molecular Cell Biology and Molecular Medicine read online next page 1143 Encyclopedia of Molecular Cell Biology and Molecular Medicine read online Home Toggle text on/off