Change label and definition: GO:0039585 PKR-mediated signaling (was:obsoletion request)

[pgaudet]

GO:0039585 PKR-mediated signaling No annotations Represents a MF

[deustp01]

In fact there is an annotation - R-HSA-9833482 "PKR-mediated signaling", released in September 2023. What does "represents a MF" means here - it definitely looks like a multi-step process to us. Are there suggestions for re-annotation, or is there a strategy question here about defining pathway boundaries better? @rwst

[rwst]

Agreed. To summarize there are more than one distinct steps in the process

• PKR dimerization
• PKR dimer autophosphorylation
• p-PKR dimer phosphorylates eIF2-alpha
• p-PKR dimer phosphorylates ~10 other proteins/complexes
• p-PKR dimer localizes to nucleus
• in nucleus, p-PKR dimer phosphorylates 2 other proteins/complexes

Which do not belong to PKR-mediated signaling?

[pgaudet]

Hi @rwst @deustp01

Thanks for the feedback, this is very useful, especially for terms with no annotations.

We aim to have beginnings and ends in the term definitions. This term was not too bad, but we could be clearer: how about f we changed the current definition:

A series of reactions in which a signal is passed on to downstream proteins within the cell via PKR (also known as EIF2AK2), an intracellular protein kinase that is activated by stress signals or upon binding to double-stranded RNA (dsRNA), followed by autophosphorylation. PKR plays a role in the antiviral response, phosphorylating proteins such as the translation initiation factor eIF2 to inhibit protein synthesis during viral infection. Begins with activation of PKR activity, and ends with regulation of a downstream cellular process, e.g. regulation of transcription or inhibition of translation

to

An intracellular signaling pathway that starts with activation of PKR (also known as EIF2AK2) upon double-stranded RNA (dsRNA) binding introduced in the cell by a viral infection. Activated PKR phosphorylates EIF2S2 (also known as eIF2alpha), and inhibits cellular translation.

Maybe we also need to change the term label to PKR/eIFalpha signaling, since PKR can activate other targets. This would ensure that we annotate that specific pathway. PMID:23354059 PMID:34305942

What do you think ?

Thanks, Pascale

[pgaudet]

@rwst With respect to the steps in PKR activation (phosphorylation, dimerization, etc), we can describe this is definitions, but we dont create specific processes for these.

Pascale

[rwst]

It's definitely more than translation regulation.

[pgaudet]

Can you propose a definition? I see there is also NF-KB activation but that seems a different role of PKR.

[rwst]

It looks like your aiming for specific starts/ends will abandon the majority of causes/effects of PKR activation. In that case, and if you concentrate on the effects on translation then PKR/eIFalpha signaling is fine.

[pgaudet]

OK thanks.

I especially dont want to make the BP mean 'any signaling pathway in which PKR plays a role', because that doesn't describe the pathway, it describes the activity.

I will reformulate as suggested above, which is consistent with the Reactome model, and we can create new terms as more pathways are described.

Thanks, Pascale

[raymond91125]

Is this good? GO:0039585 PKR/eIFalpha signaling "A series of reactions in which a signal is passed on to downstream proteins within the cell via PKR (also known as EIF2AK2), an intracellular protein kinase that is activated by stress signals or upon binding to double-stranded RNA (dsRNA), followed by autophosphorylation. PKR plays a role in the antiviral response, phosphorylating proteins such as the translation initiation factor eIF2 to inhibit protein synthesis during viral infection. Begins with activation of PKR activity, and ends with inhibition of translation"

[rwst]

Looks fine, thanks!

[pgaudet]

Move PKR/eIFalpha signaling as is_a intracellular signaling cassette