NTR GPCR transactivation

[gocentral]

Hi,

I'd like to request a new molecular function term please for G protein-coupled receptor transactivation.

Suggested definition: The process in which a receptor is activated by another receptor.

I'm not sure where this would fit in the ontology: is a GO:0004930 G-protein coupled receptor activity, part of GO:0005515 Protein Binding and GO:0008277 regulation of G-protein coupled receptor protein signaling pathway?

This is one of the first references for the phenomenon: http://www.jbc.org/content/278/43/42578.long But it has since then been observed for many different GPCRs and can occur both between homo-oligomers as well as hetero-oligomers....it can also have an inhibitory effect if one receptor is bound to an inverse agonist, and the other an antagonist (for instance in the chemokine receptors, CXCR4 and 7).

Reported by: antonialock

Original Ticket: geneontology/ontology-requests/8921

[gocentral]

• labels: --> signaling

Original comment by: antonialock

[gocentral]

Hi Antonia,

We have a receptor transactivation term which would be the most suitable parent:

receptor transactivation ; GO:0035624 The process in which a receptor is activated via signaling events from a receptor for a different ligand. Receptor transactivation is an example of cross-talk between signaling pathways and can occur through several different mechanisms.

Does the definition hold true for a GPCR transactivation term (where the transactivation is within a dimer)?:

G-protein coupled receptor transactivation ; GO:NEW The process in which a G-protein coupled receptor is activated via signaling events from a G-protein coupled receptor for a different ligand. is_a: receptor transactivation ; GO:0035624 is_a: positive regulation of G-protein coupled receptor protein signaling pathway ; GO:0045745

Original comment by: rebeccafoulger

[gocentral]

• assigned_to: nobody --> rfoulger

Original comment by: rebeccafoulger

[gocentral]

Hi Becky,

I saw that term, but it is not entirely true because transactivation can occur between receptors for the same ligand. It is also a "process" term, but surely it could also be a 'function"? It doesn't necessarily have to represent cross-talk either but could be used for signal amplification.

Cheers, Antonia.

Original comment by: antonialock

[gocentral]

Hi Antonia,

I need to do a bit more reading on how the receptor dimer parts activate eachother on this one. Don't worry too much about the process v. function distinction: it's quite an artificial distinction for some nodes, hence the process-function links we're adding in.

Original comment by: rebeccafoulger

[gocentral]

Okay... here's my (multi-part) suggestion. Feel free to suggest any revisions/improvements.

1. Create CC terms for the dimeric GPCR complexes: receptor complex ; GO:0043235 --%G-protein coupled receptor dimeric complex ; GO:NEW1 ----%G-protein coupled receptor heterodimeric complex ; GO:NEW2 ----%G-protein coupled receptor homodimeric complex ; GO:NEW3

2. Broaden definition of receptor transactivation ; GO:0035624 (0 direct annotations) receptor transactivation ; GO:0035624 The process in which a receptor is activated via signaling events from a receptor for a different ligand. Receptor transactivation is an example of cross-talk between signaling pathways and can occur through several different mechanisms. > The process in which a receptor is activated by another receptor. Receptor transactivation can occur through different mechanisms and includes cross-talk between signaling pathways where one receptor activates a receptor for a different ligand, and also activation of subunits within a receptor oligomer.

3. Make a new term: cross-receptor activation within G-protein coupled receptor heterodimer ; GO:NEW4 Activation of one promoter of a G-protein coupled receptor (GPCR) heterodimer by the associated subunit. For example, agonist occupancy in one protomer of a GPCR heterodimer may activate the associated protomer. is_a: receptor transactivation ; GO:0035624 part_of: dimeric G-protein coupled receptor signaling pathway ; GO:NEW6 PMID: 21063387

4. Make a new term for the chemokine receptors: cross-receptor inhibition within a G-protein coupled receptor dimer ; GO:NEW5 Inhibition of one promoter of a G-protein coupled receptor (GPCR) heterodimer by the associated subunit. For example, agonist activation of one subunit of some cytokine receptor heterodimers can prevent activation of the associated cytokine receptor subunit. PMID:15979374

5. Make a new term for the signaling through the GPCR dimer: dimeric G-protein coupled receptor signaling pathway ; GO:NEW6 synonym: G-protein coupled receptor signaling pathway via GPCR dimer is_a: G-protein coupled receptor signaling pathway ; GO:0007186 Any series of molecular signals initiated by an extracellular signal combining with a dimeric receptor on the surface of the target cell, and proceeding with the activated receptor promoting the exchange of GDP for GTP on the alpha-subunit of an associated heterotrimeric G-protein complex. Heterodimeric and homodimeric GPCRs may have different functional properties from those of the respective monomers, E.g. heterodimers may recruit specific G-proteins different from those recruited by homodimers or monomers.

NB: I'm deliberately staying away from the homodimerization activity terms as theses are up for discussion.

Becky

Original comment by: rebeccafoulger

[gocentral]

I'll implement this tomorrow (Wednesday 2nd Nov) if there's no objections.

Thanks Becky

Original comment by: rebeccafoulger

[gocentral]

New terms added:

G-protein coupled receptor dimeric complex ; GO:0038037 G-protein coupled receptor homodimeric complex ; GO:0038038 G-protein coupled receptor heterodimeric complex ; GO:0038039 cross-receptor activation within G-protein coupled receptor heterodimer ; GO:0038040 cross-receptor inhibition within G-protein coupled receptor heterodimer ; GO:0038041 dimeric G-protein coupled receptor signaling pathway ; GO:0038042

Go ahead and submit a new SF item if you require any further terms. Thanks Becky

Original comment by: rebeccafoulger

[gocentral]

• status: open --> closed-accepted

Original comment by: rebeccafoulger