GO:0060238 and GO:0010969

[gocentral]

Hi,

I wonder whether the two terms GO:0060238 (Any process that modulates the rate, frequency or extent of pheromone-dependent signal transduction during conjugation with cellular fusion, the series of molecular signals that bring about the relay, amplification or dampening of a signal generated in response to a cue, such as starvation or pheromone exposure, in organisms that undergo conjugation with cellular fusion.)

and GO:0010969 (Any process that modulates the frequency, rate or extent of pheromone-dependent signal transduction during conjugation with cellular fusion, a signal transduction process resulting in the relay, amplification or dampening of a signal generated in response to pheromone exposure in organisms that undergo conjugation with cellular fusion.)

should be sibling terms rather than parent/child? My reasoning is that different regulators that require pheromone in order to regulate conjugation may or may not regulate conjugation in the absence of pheromone (some regulators are transcriptionally activted as part of the signalling cascade and some are not).

Reported by: antonialock

Original Ticket: geneontology/ontology-requests/8919

[gocentral]

just to clarify: I have had a few cases where both happens (regulates both basal activity as well as the response to pheromone) and there I would like to annotate to both terms.

Original comment by: antonialock

[gocentral]

pps. or possibly add another term for regulation of "pheromone independent" signal transduction

Original comment by: antonialock

[gocentral]

Hi Antonia,

It looks like the definition of GO:0060238 needs to be tweaked to remove the 'pheromone' text (it probably got there by a copy-and-paste error).

It's fine to annotate to both the parent and child. In terms of making a new term, x-independent terms aren't good ontology practise. If the cue isn't a pheromone, what else is the trigger?

thanks Becky

Original comment by: rebeccafoulger

[gocentral]

Hi Becky,

There were three reasons for my request:

Firstly I thought it's unintuitive to annotate to both a parent and a child term seeing that the child term is supposedly more specific than the parent, so by definition shouldn't it encompass all that the parent encompass?

The second reason is that in pombe, the pheromone GPCR Mam2 appears to sequester the G-alpha thereby actively prevent spontaneous signalling in the absence of ligand.

Thirdly you also get a certain amount of "basal" activity (the notion that GPCRs exist in a state of dynamic equilibrium between on and off - binding of agonist merely shifts the equilibrium towards "on". You also get constitutively active mutants (see http://www.nature.com/nrd/journal/v1/n8/full/nrd872.html for a review).

I suppose for these reasons I didn't think that the structure/order of the terms in the ontology were very intuitive.

Original comment by: antonialock

[gocentral]

Hi Antonia,

Ah- so it's not a different ligand that's starting the signaling, it's the absence of a ligand. This relates to a recent discussion on the dependence receptors. I'll add in a term for starters:

signal transduction in absence of ligand ; GO:NEW1 is_a: signal transduction Def: A series of molecular signals initiated by the absence of a ligand or the withdrawal of a ligand from a receptor. synonym: dependence receptor signaling pathway BROAD synonym: addiction receptor signaling pathway [PMID: 15044679] BROAD synonym: nonclassical signal transduction [PMID 15044679] BROAD synonym: negative signal transduction [PMID 15044679] EXACT

For a receptor that is preventing signaling: if the signal isn't being passed on it should be annotated to a negative regulation of signal transduction term.

Becky

Original comment by: rebeccafoulger

[gocentral]

Ah ok, cheers.

Could "basal activity" also be a synonym?

Original comment by: antonialock

[gocentral]

indeed it can. I've added 'basal signaling' synonyms to the following two new terms:

signal transduction in absence of ligand ; GO:0038034 G-protein coupled receptor signaling in absence of ligand ; GO:0038035

And put a comment in GO:0038035 to say that the term is intended for use by GPCRs that signal at a basal level in the absence of agonist-binding.

Original comment by: rebeccafoulger

[gocentral]

super, thanks!

Original comment by: antonialock

[gocentral]

no problem. I might have to tweak the definitions of signal transduction and the relevant signaling pathways to accomodate these terms, as most of the definitions start with ligand-binding to a receptor. Then I can add GO:0038035 under the GPCR signaling pathway terms too..... on the list.

Original comment by: rebeccafoulger

[gocentral]

• status: open --> pending

Original comment by: rebeccafoulger

[gocentral]

GPCR signaling pathway terms have been suitably tweaked to allow signaling in the absence of a ligand.

So the relationship is in: G-protein coupled receptor signaling pathway ; GO:0007186 --[isa]G-protein coupled receptor signaling in absence of ligand ; GO:0038035

Am closing this SF item. Go ahead and submit a fresh ticket if there's anything else. Thanks.

Original comment by: rebeccafoulger

[gocentral]

• status: pending --> closed-accepted

Original comment by: rebeccafoulger