From The functional genomic response of developing embryonic submandibular glands to NF-kappaB inhibition
BMC Developmental Biology
BMC Developmental Biology
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Connections Map. This signaling map reflects the pathways investigated in SMGs. Known and putative connections are based on references [6], [11], [23], [36], [76]-[108].
- These SMG cellular and extracellular components may be visualized as a Connections Map which details the functional relationships within and between pathways (Fig. 1).
- Complex networks of biological signaling pathways (Fig. 1) emerge from the interconnections of simple pathways under local control [15-17].
- With the present experiments, we sought a glimpse of the extraordinarily complex behaviors of a focused signaling network (Fig. 1).
- Of these, we focused our attention on those signal transduction, cell cycle, and apoptosis transcripts related to the Connections Map (Fig. 1).
- Cyclin D2, Cdc25a, and PCNA promote cell division; p57 inhibits cell division (Fig. 1).
- BMPs inhibit cell proliferation via downstream Smad1/5/8 proteins whereas Smad7 inhibits TGF-β and activin signaling (Fig. 1).
- Further, we utilized PNN analysis to determine the iterated composite relative importance among Connections Map (Fig. 1) transcripts which have altered expression as a consequence of inhibition of NF-κB translocation into the nucleus (Fig. 10).
- The declining PCNA and GR reflect the sharp decline in cell proliferation and branching; the increasing BMP1 and BMP3b similarly reflects inhibition of cell proliferation (Fig. 1).
- As shown in Table 2, we find 18 proteins which have both a 1.5-fold or greater change with NF-κB inhibition and are specifically related to the Connections Map (Fig. 1).
- Raf plays a key role in the Ras signaling pathway (Fig. 1).
- Further, both the SHP-2/Ras and JAK/STAT3 pathways are activated by IL-6R/gp130 signaling (Fig. 1).
- Considering the outcome of this study relative to the Connections Map (Fig. 1), it is apparent that NF-κB nuclear translocation is functionally integral to a genetic network with broadly related, rather than independent, components.
- Specifically, we assigned those genes related to the Connections Map (Fig. 1) that have a 1.5 or greater fold-change to functional groups (i.e., cell cycle, apoptosis, signal transduction, etc.) which have biological significance.
- We used PNN analyses to determine which Connection Map (Fig. 1) transcripts or proteins with altered expression best discriminate CONT from SN50-treated explants with 100% sensitivity and specificity [69].