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PMID: 8981359
This
report will focus on our attempts to understand some of
the signal transduction pathways that lead from the
interaction of CSF-1 with its receptor to subsequent
DNAsynthesis a few hours later.
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PMID: 8981359, 6967488
CSF-1 increases plasminogen activator
expression in murine macrophages (Hamilton et al.,
1980).</csml:comment>
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PMID: 8981359
This
report will focus on our attempts to understand some of
the signal transduction pathways that lead from the
interaction of CSF-1 with its receptor to subsequent
DNAsynthesis a few hours later.

These results suggested that
in most CSF-1–treated BMM cultures, there was an
induction of IFNa/b which could influence the results
by suppressing the level of DNA synthesis
 measured.
We confirmed that CSF-1
could also induce low levels of IFNa/b production, as a
cell-associated activity, in CBA BMM cell cultures.

When an
antibody to type I IFN was included, there was a
regular increase in the rate of DNA synthesis in response
to CSF-1 </csml:comment>
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PMID: 8981359
We confirmed that CSF-1
could also induce low levels of IFNa/b production, as a
cell-associated activity, in CBA BMM cell cultures.</csml:comment>
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PMID: 8981359
IFNalpha/beta bind their corresponding receptor.</csml:comment>
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PMID: 8981359
The
inhibitors that we have used include dimethylamiloride
(DMA) (which inhibits the Na1/H1 antiporter), IFNg,
lipopolysaccharide (LPS), tumor necrosis factor a
(TNFa), and a number of compounds that raise intracellular
cAMP levels. These agents, which apparently
have nothing in common, all suppress macrophage
DNA synthesis.</csml:comment>
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</csml:comment>
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<csml:comment type="text">

PMID: 8981359
IFN-gamma binds its receptor.</csml:comment>
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</csml:comment>
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indirect</csml:comment>
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<csml:comment type="text">

</csml:comment>
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<csml:comments>
<csml:comment type="text">


PMID: 8981359
The
inhibitors that we have used include dimethylamiloride
(DMA) (which inhibits the Na1/H1 antiporter), IFNg,
lipopolysaccharide (LPS), tumor necrosis factor a
(TNFa), and a number of compounds that raise intracellular
cAMP levels. These agents, which apparently
have nothing in common, all suppress macrophage
DNA synthesis.

In a BAC1.2F5 cell line
containing the control vector, the addition of IFNg or
8Br-cAMP inhibited the increase in DNA synthesis in
response to CSF-1

PMID: 8981359
Studies were done to determine the effects of LPS,
TNFa, IFNg, and 8Br-cAMP on the proliferation of
BMM from wild-type mice compared with cells from the
IFNAR-1 2/2 mice. As before, all agents suppressed
DNAsynthesis in the wild-type system.</csml:comment>
</csml:comments>
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<csml:comment type="text">

</csml:comment>
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PMID: 8981359
LPS binds its corresponding receptor</csml:comment>
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</csml:comment>
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PMID: 8981359
TNF-alpha binds its corresponding receptor.</csml:comment>
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indirect</csml:comment>
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</csml:comment>
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PMID: 8981359
The
inhibitors that we have used include dimethylamiloride
(DMA) (which inhibits the Na1/H1 antiporter), IFNg,
lipopolysaccharide (LPS), tumor necrosis factor a
(TNFa), and a number of compounds that raise intracellular
cAMP levels. These agents, which apparently
have nothing in common, all suppress macrophage
DNA synthesis.

We propose that LPS and
TNFa inhibit DNA synthesis, at least in part, through
their induction of endogenous type I IFN.
This proposition
is supported by the fact that an antibody to type I
IFN could partially reverse their inhibitory effects on
CBABMM.</csml:comment>
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indirect</csml:comment>
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<csml:comment type="text">
PMID: 8981359
The
inhibitors that we have used include dimethylamiloride
(DMA) (which inhibits the Na1/H1 antiporter), IFNg,
lipopolysaccharide (LPS), tumor necrosis factor a
(TNFa), and a number of compounds that raise intracellular
cAMP levels. These agents, which apparently
have nothing in common, all suppress macrophage
DNA synthesis.</csml:comment>
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indirect</csml:comment>
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indirect</csml:comment>
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<csml:comment type="text">

PMID: 8981359
We propose that LPS and
TNFa inhibit DNA synthesis, at least in part, through
their induction of endogenous type I IFN.</csml:comment>
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</csml:comment>
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indirect</csml:comment>
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<csml:comment type="text">

</csml:comment>
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PMID: 8981359, 7761098
We have shown that IFNg can reduce the CSF-1–
dependent c-myc mRNA expression.</csml:comment>
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<csml:comment type="text">

</csml:comment>
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</csml:comment>
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<csml:comments>
<csml:comment type="text">

</csml:comment>
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<csml:comment type="text">


PMID: 8981359
Rb is a member of a family of
tumor suppressor proteins that interact with transcription
factors such as the E2F family.</csml:comment>
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<csml:comment type="text">

</csml:comment>
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</csml:comment>
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<csml:comment type="text">


PMID: 8981359, 1534305
For example, it is
believed that Rb sequesters E2F-1 from the DNA, thus
inhibiting its transcriptional activity.
When Rb is phosphorylated, it releases E2F-1 which is
then able to activate the transcription of genes.</csml:comment>
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<csml:comment type="text">

indirect</csml:comment>
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</csml:comment>
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PMID: 8981359
One of the known signal transduction systems that we
have studied is the cyclin D/cdk system. This kinase system is believed to control retinoblastoma protein
(Rb) phosphorylation.

PMID: 8981359, 1534305
For example, it is
believed that Rb sequesters E2F-1 from the DNA, thus
inhibiting its transcriptional activity.
When Rb is phosphorylated, it releases E2F-1 which is
then able to activate the transcription of genes.

PMID: 8981359
The
addition of LPS, 8Br-cAMP, DMA, or IFNg resulted in
suppression of the degree of Rb phosphorylation.</csml:comment>
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</csml:comment>
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</csml:comment>
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</csml:comment>
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<csml:comments>
<csml:comment type="text">


PMID: 8981359, 1534305
For example, it is
believed that Rb sequesters E2F-1 from the DNA, thus
inhibiting its transcriptional activity.
When Rb is phosphorylated, it releases E2F-1 which is
then able to activate the transcription of genes.</csml:comment>
</csml:comments>
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indirect</csml:comment>
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<csml:comment type="text">


PMID: 8981359, 1534305
For example, it is
believed that Rb sequesters E2F-1 from the DNA, thus
inhibiting its transcriptional activity.
When Rb is phosphorylated, it releases E2F-1 which is
then able to activate the transcription of genes.</csml:comment>
</csml:comments>
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indirect</csml:comment>
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<csml:comment type="text">


PMID: 8981359
Some of
the genes that are believed to be controlled by the E2F
family of transcription factors are important for cell cycle progression. including thymidine kinase, dihydrofolate
reductase, and c-myc. </csml:comment>
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indirect</csml:comment>
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<csml:comments>
<csml:comment type="text">


PMID: 8981359
Some of
the genes that are believed to be controlled by the E2F
family of transcription factors are important for cell cycle progression. including thymidine kinase, dihydrofolate
reductase, and c-myc. </csml:comment>
</csml:comments>
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indirect</csml:comment>
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PMID: 8981359
Some of
the genes that are believed to be controlled by the E2F
family of transcription factors are important for cell cycle progression. including thymidine kinase, dihydrofolate
reductase, and c-myc. </csml:comment>
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PMID: 8981359
The PI3-kinase was tyrosine phosphorylated soon
after adding CSF-1 to the BMM.</csml:comment>
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<csml:comment type="text">


PMID: 8981359
c-fms was also immunoprecipitated
and tyrosine phosphorylated, in addition
to a number of proteins which we are now trying to
identify.</csml:comment>
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<csml:comment type="text">


PMID: 8981359
c-fms was also immunoprecipitated
and tyrosine phosphorylated, in addition
to a number of proteins which we are now trying to
identify.</csml:comment>
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PMID: 8981359
These results suggest
that, in response to CSF-1, PI3-kinase is tyrosine
phosphorylated, and that other proteins associate with
PI3-kinase, in addition to c-fms, to form a complex.</csml:comment>
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PMID: 8981359
In contrast, rapamycin, an inhibitor of S6
kinase, inhibited CSF-1-induced DNA synthesis in
BAC1.2F5 cells, suggesting that this kinase may be a
part of the critical signaling pathway(s).</csml:comment>
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PMID: 8981359
However,
there was a synergistic inhibition of DNA synthesis by
the combination of wortmannin and rapamycin.</csml:comment>
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PMID: 8981359
These results suggest that STAT1
and STAT3 are activated in the BAC1.2F5 cells in
response to CSF-1.</csml:comment>
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PMID: 8981359
These results suggest that STAT1
and STAT3 are activated in the BAC1.2F5 cells in
response to CSF-1.</csml:comment>
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PMID: 8981359
JAK kinases can be activated by IFNa/b or IFNg,
and the presumed substrates for these kinases are the
STAT proteins.</csml:comment>
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PMID: 8981359
JAK kinases can be activated by IFNa/b or IFNg,
and the presumed substrates for these kinases are the
STAT proteins.</csml:comment>
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<csml:comments>
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<csml:comment type="text">


PMID: 8981359
We also have evidence that Tyk2 is tyrosine
phosphorylated after c-fms activation.</csml:comment>
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PMID: 8981359
JAK kinases can be activated by IFNa/b or IFNg,
and the presumed substrates for these kinases are the
STAT proteins. The STAT proteins can form homodimers
or heterodimers when they are tyrosine phosphorylated,
and they can effect DNA transcription through
certain DNA response elements in IFN-responsive
genes.</csml:comment>
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PMID: 8981359
JAK kinases can be activated by IFNa/b or IFNg,
and the presumed substrates for these kinases are the
STAT proteins. The STAT proteins can form homodimers
or heterodimers when they are tyrosine phosphorylated,
and they can effect DNA transcription through
certain DNA response elements in IFN-responsive
genes.</csml:comment>
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PMID: 8981359
JAK kinases can be activated by IFNa/b or IFNg,
and the presumed substrates for these kinases are the
STAT proteins. The STAT proteins can form homodimers
or heterodimers when they are tyrosine phosphorylated,
and they can effect DNA transcription through
certain DNA response elements in IFN-responsive
genes.</csml:comment>
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PMID: 8981359
JAK kinases can be activated by IFNa/b or IFNg,
and the presumed substrates for these kinases are the
STAT proteins. The STAT proteins can form homodimers
or heterodimers when they are tyrosine phosphorylated,
and they can effect DNA transcription through
certain DNA response elements in IFN-responsive
genes.</csml:comment>
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indirect</csml:comment>
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PMID: 8981359
We confirmed that CSF-1
could also induce low levels of IFNa/b production, as a
cell-associated activity, in CBA BMM cell cultures.</csml:comment>
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PMID: 8981359
IFNalpha/beta bind their corresponding receptor.</csml:comment>
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PMID: 8981359
We propose that LPS and
TNFa inhibit DNA synthesis, at least in part, through
their induction of endogenous type I IFN.</csml:comment>
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PMID: 8981359
We propose that LPS and
TNFa inhibit DNA synthesis, at least in part, through
their induction of endogenous type I IFN.</csml:comment>
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PMID: 8981359
We propose that LPS and
TNFa inhibit DNA synthesis, at least in part, through
their induction of endogenous type I IFN.</csml:comment>
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