468
Cellular Interactions
bound to one or more of the calmodulin
binding sites. This association activates
thekinaseandpermitsphosphorylationon
serine/threonine at consensus phosphory-
lation sites. Once CaM KII is activated
it can undergo autophosphorylation on
T286/287. Consequently, it can maintain
its state of activation after the calmod-
ulin dissociates from CaM KII. CaM KII
is thought to be involved with the transi-
tion from metaphase to anaphase in both
somatic cells and in eggs. There is gen-
eral agreement from many sources that
the rise in intracellular-free calcium in
amphibian eggs activates CaM KII, which
then activates the ubiquitin-dependent cy-
clin degradation pathway and also acts
on c-mos degradation. At egg activation,
an increase in activity of CaM KII can
be measured in mammalian eggs. By us-
ing antibodies that bind to the
β
-an
d
δ
-isotypes of CaM KII, it has been revealed
that speciFc molecular scaffolds in the egg
and early mouse embryo are enriched with
CaM KII, as will be discussed in subse-
quent sections.
One
well-studied
calcium-dependent
event involves inactivation of MP±. MP±
is composed of cyclin B1 and p34
cdc2
and
has been indicated as one of the kinases
that drive the cell into metaphase. The rise
in intracellular-free calcium that accompa-
nies fertilization inactivates MP± by target-
ing cyclin B1 for degradation through an
ubiquitin-dependent proteolytic pathway.
MP± activity decreases in the absence of
cyclin B1.
2
Coordination of Complex Signaling
Pathways
There are numerous signaling pathways
involved in the conversion of the egg to
the zygote as outlined in an earlier section.
These pathways act in a particular temporal
sequence and some of the pathways appear
to act on the same structure at different
times progressively changing the cellular
components. This is the case for the forma-
tion of the second polar body, which will be
described in more detail in a subsequent
section. The complexity of the changes
that occur is not indicative of a system
in which enzymes and speciFcally kinases
are randomly diffused about the cells, but
rather of a situation in which kinases and
other components have restricted domains
within the cells. Two features of the mouse
egg are likely to permit the existence of
these restricted domains, that is, (1) the
meiotic spindle appears to be serving as a
molecular scaffold that anchors elements
of different signaling pathways; (2) the
architecture of the egg itself is highly po-
larized and may restrict the distribution of
signaling components including kinases.
2.1
Molecular Scaffolds
The potential for the meiotic spindle to
serve as a molecular scaffold provides the
opportunity to study the regulation of, and
cross talk among, distinct cytoplasmic sig-
naling pathways in mammalian eggs. MAP
kinase pathways and their association with
molecular scaffolds have received much
study. Such scaffolds, originally identiFed
in yeast as the Ste5 protein, have been
shown to bring together many of the up-
stream regulatory elements in the MAP
kinase pathway. Proteins with functional
similarities to Ste5 have been identiFed in
higher eukaryotes. Of particular relevance
to this review, microtubules have been
shown to serve as a molecular scaffold
for a variety of signaling pathways includ-
ing elements of MAP kinase pathways.
previous page 1142 Encyclopedia of Molecular Cell Biology and Molecular Medicine read online next page 1144 Encyclopedia of Molecular Cell Biology and Molecular Medicine read online Home Toggle text on/off