April 19th 2010
From GO Public
Present: Becky, Val, Sandra, Ruth, Alex.
AI1: It was decided Becky will merge intracellular signaling cascade ; GO:0007242 AND signal transmission via intracellular cascade ; GO:0023013into intracellular signaling pathway ; GO:0023034 (no direct annotations). We didn't disucss it, but unless I hear objections, I'll just keep the signaling pathway parent and remove it from the signaling process bit of the tree.
AI2: Lots of terms under GO:0023034/GO:0007242 should be given the 'intracellular receptor-mediated signaling pathway ; GO:0030522' parent instead. Blue-light signaling is one such example. If you come across others, please let me know and I'll move them. This should clear up this section a bit. Becky will also clear up redundant parentage.
AI2.1: Rename protein kinase cascade as intracellular protein kinase cascade.
AI3: Once the top level terms are ironed out, in the future we can create new terms 'intracelluar signal transduction downstream of cell surface receptor' and e.g. 'MAPKKK signaling downsream of EGF receptor' to link the intracellular signaling downstream of the cell membrane and make more complete 'pathways'.
AI4: Rename 'regulation of signal transduction ; GO:0009966' to 'regulation of signaling pathway GO:0009966' and move it to the signaling part of the tree.
AI5: For regulation terms that aren't regulation of a pathway (eg regulation of receptor activity ; GO:0010469) move them to be direct children of 'regulation of signaling process ; GO:0023051'.
AI6: In the future we can create terms for regulation of each bit of the signaling process (signal formation, transport, intracellular transduction etc).
INITIATION OF SIGNAL TRANSDUCTION ; GO:0023036
AI7: Add synonym 'signal reception' to initiation of signal transduction ; GO:0023036.
SIGNAL RELEASE AND SIGNAL GENERATION
The main things from the discussion is that we can't make signal release a direct child of cell secretion, because of passive diffusion etc, so they'll just remain connected via dual-parentage of the children at the moment.
Also there was alot of discussion about what we mean by 'cell-cell signaling'. Its current definition is restricted to signaling from one cell to A DIFFERENT CELL. This means we have to create more generic terms to include autocrine signaling.
AI7: Ask David Hill if he would object to the 'cell-cell' signaling bit being removed from the term, and it being moved out from under cell-cell signaling. It currently has the exact synonym 'signal generation'.
AI8: Depending on the outcome of the conversation with David, we might need to open up the discussion to the rest of the consortium about whether cell-cell signaling should be restricted to 2 DIFFERENT cells.
Can't make any other changes at the moment, until the above 2 are solved.
STEROID HORMONE VS STEROID HORMONE RECEPTOR
Although they should be linked, Ruth and Alex pointed out that we should look to see how the terms are being used in annotation to see if there's a reason why they're separate. Ruth pointed out that it might be to do with the fact that some hormones signal via multiple receptors. steroid hormone receptor activity is currently a part_of 'steroid hormone mediated signaling pathway ; GO:0043401' not 'steroid hormone receptor signaling pathway ; GO:0030518' so that's a bit odd.
The definition of GO:0030518 also seems the wrong way round: steroid hormone receptor signaling pathway ; GO:0030518 Any series of molecular signals generated as a consequence of a steroid hormone binding to its receptor. It should be '... as a consequence of a steroid hormone receptor binding to one of its physiological ligands'.
AI9: Becky to look into how the terms are being used in annotation and report back.
FOR PROCESSES UPSTREAM OF LIGAND-RECEPTOR BINDING Since the current definition of the receptor-mediated pathway terms begin at receptor-ligand binding, it currently creates TPVs for events upstream of R-L binding (eg processing of the receptor Notch prior to ligand binding). Becky previously suggested expanding the definitions to include upstream events. However, Notch signaling pathway is used synonymously with Notch signaling transduction, and transduction does start at the membrane. Therefore, Becky suggested instead making these upstream events an instance of 'regulation of x pathway'.
FOR NEXT TIME....... This led us onto Ruth's point that we need to discuss in the next meeting: How to define, name and place terms where the receptor binds to multiple ligands, or a ligand binds to multiple receptors. We'll need to check for TPVs with receptor terms being children of the signaling process terms.
We have the following intracellular signaling terms at the moment:
- intracellular signaling pathway ; GO:0023034 (no direct annotations)
- intracellular signaling cascade ; GO:0007242
- intracellular receptor-mediated signaling pathway ; GO:0030522
- signal transmission via intracellular cascade ; GO:0023013
Q: do all signaling pathways have to have a receptor?
Q: can I just merge GO:0007242 into GO:0023034, and remove it from under the signal transduction part of the tree?
Q: should all the x-mediated terms really be under intracellular pathway?
Q: How does GO:0023013 fit in? Does it mean intracellular signaling downstream of a receptor?
We need to move the 'regulation of x signaling pathway' terms to the signaling pathway bit of the tree. The trouble is that other 'regulation of' terms are mixed in there that aren't 'regulation of a pathway':
- regulation of MAP kinase activity ; GO:0043405
- regulation of receptor activity ; GO:0010469
- regulation of receptor recycling ; GO:0001919
I would propose: 1/ renaming 'regulation of signal transduction ; GO:0009966' to 'regulation of signaling pathway GO:0009966; 2/ Moving the renamed GO:0009966, to be a child of 'signaling pathway ; GO:0023033' 3/ Keeping all the regulation of x signaling pathway terms under GO:0023033. 4/ Moving GO:0010469 and GO:0001919 to be direct children of 'regulation of signaling process ; GO:0023051'
AI: We'd need to go through and see which others should be a child of GO:0023033 instead.
Q: do we need a 'regulation of signal transduction' term in the 'regulation of signal process' part of the tree? Signaling pathways have multiple steps at which regulation can occur..
- signal formation
- signal release
- signal transport
- signal reception
- signal transduction
Do we want regulation terms for each?
The complication comes because the signaling pathway terms at the moment begin at the receptor (eg signal transduction). Do we have the individual regulation of x. pathway terms under signal transduction too? (ie where we're just removed them from).
initiation of signal transduction ; GO:0023036
Is this signal reception?
SIGNAL RELEASE AND SIGNAL GENERATION
We need to link the terms: signal release ; GO:0023061 generation of a signal involved in cell-cell signaling ; GO:0003001 secretion by cell ; GO:0032940
Q: is signal release ALWAYS secretion? (ie can we have signal release ; GO:0023061 as a child of secretion by cell ; GO:0032940?.
We could have something like:
generation of a signal ; GO:NEW (covers formation, release and transport to right place, based on existing term)
--%generation of a signal involved in cell-cell signaling ; GO:0003001
----<release of a signal involved in cell-cell signaling ; GO:NEW
--<signal release ; GO:0023061
----%release of a signal involved in cell-cell signaling ; GO:NEW
Q:How to link to secretion by cell though? Q:Is secretion by cell too specific. Do we need to go up to 'secretion'? Q:If we don't link the secretion and signal release terms, which children do we transfer?
STEROID HORMONE VS STEROID HORMONE RECEPTOR
Can we merge these pairs: is it okay to have steroid hormone receptor signaling pathway under 'hormone-mediated signaling pathway'??
steroid hormone mediated signaling pathway ; GO:0043401
steroid hormone receptor signaling pathway ; GO:0030518
glucocorticoid mediated signaling pathway ; GO:0043402
glucocorticoid receptor signaling pathway ; GO:0042921