Cellular Interactions
469
For example, the MAP kinases ERK1/2
have been shown to associate with micro-
tubules. In another MAP kinase pathway,
the JNK pathway, elements of that pathway
(i.e. MLK2, the MAP kinase kinase kinase)
associate with the microtubules through
kinesin-like molecular motors.
Molecular scaffolds have been investi-
gated in a wide variety of systems and
signaling pathways. Results from these
studies have led to the identi±cation of
the following putative roles for molecu-
lar scaffolds: (1) increase the ef±ciency of
cellular reactions by optimally positioning
kinases as well as their substrates and
products on the scaffold; (2) decrease the
response time to a stimulus; (3) enhance
some forms of cross talk among pathways
while reducing other forms of cross talk
(by juxtaposing elements of distinct path-
way
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substrate speci±city and; (5) localize sig-
naling pathways to speci±c parts of a cell.
All of these putative roles would serve use-
ful functions in mammalian eggs since
eggs must undergo a highly orchestrated
regime of changes rapidly after fertiliza-
tion and in the absence of new gene
transcription.
There are a number of potential ad-
vantages in employing microtubules as
scaffolds in mammalian eggs. First, in
the mammalian egg, microtubules pro-
vide a relatively large structure that can
serve as a large surface area for the bind-
ing of various proteins and components
of signaling pathways. Second, the micro-
tubules in M-phase cells exhibit a distinct
polarity with their disassembly end embed-
ded in the centrosome and the assembly
end closer to the cell equator (for kine-
tochore and polar microtubules). Should
elements of a signaling pathway be as-
sociated with a molecular motor protein
or activated by something carried on a
molecular motor protein, they could be
positioned precisely. Third, there are three
forms of spindle microtubules, namely,
kinetochore, polar, and astral (in mouse
eggs astral microtubules are not promi-
nent) that may serve distinct functions
for signaling pathways (for example, in
the formation of midzone microtubules or
in cytokinesis). Fourth, the spindle pro-
gresses through distinct, time-dependent
changes after fertilization, which can serve
to temporarily reposition the scaffold and
associated signaling components to dis-
tinct locations in the cell at distinct times
over the ±rst 1 to 1.5 h postfertilization.
Fifth, after fertilization, the meiotic spin-
dle and its derivatives occupy a polarized
location in the egg and forming zygote. All
of these potential functions of the spin-
dle microtubules as a molecular scaffold
regulating cytoplasm signaling pathways
could serve to orchestrate the hierarchi-
cal regime of structural and functional
changes the egg undergoes in a precise
spatial and temporal order as it becomes
the zygote.
Studies in other systems provide evi-
dence to demonstrate interactions between
CaM KII and MAP kinase. For example,
CaM KII has been shown to regulate the
activity of MAP kinase in smooth muscle
tissue although the mechanism of action
was not determined. One study examin-
ing vascular smooth muscle cells shows
that CaM KII acts upstream of ERK 1/2
through a tyrosine kinase. In neurons,
CaM KII and MAP kinase colocalize on
a scaffold (i.e. the postsynaptic density)
and interact. The work on smooth muscle
and neurons, together with our own pre-
liminary studies, is very suggestive of an
interaction between CaM KII and MAP ki-
nase, or one of the upstream regulators, on
the meiotic spindle (i.e. scaffold) in mouse
eggs.
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