Signaling 2013-10-28

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A signaling call to catch up on where the signaling revisions are up to and what needs to be done next.

MONDAY 28TH OCTOBER 2013

  • 3:30pm UK time
  • 11:30am East Coast
  • 8:30am West Coast


Attendees: Becky, David H, David OS, Chris, Tanya, Judy


AGENDA: OUTSTANDING SIGNALING ISSUES


INTRACELLULAR CASSETTES

Need to define the start and stop points of these, and clarify what we mean by them. [[1]]

phosphatidylinositol 3-kinase cascade ; GO:0014065

protein kinase A signaling cascade ; GO:0010737

protein kinase B signaling cascade ; GO:0043491

protein kinase C signaling cascade ; GO:0070528

JAK-STAT signaling cascade ; GO:0007259

TOR signaling cascade ; GO:0031929

hippo signaling cascade ; GO:0035329

PKR signal transduction ; GO:0039585

stress-activated protein kinase signaling cascade ; GO:0031098

cAMP-mediated signaling ; GO:0019933

LINKING INTRACELLULAR CASSETTES TO UPSTREAM RECEPTORS

Is it worth creating GO terms to link the signaling pathways with the intracellular cassette? What would we annotate to them?

Or do we just wait for LEGO?

[[2]]



RECEPTOR AGONISTS

The term 'receptor agonist activity ; GO:0048018' has only one child (death receptor agonist activity). How can we expand this node?

If we have 'EGFR agonist', do we mean a ligand that activates the GENE PRODUCT 'Egfr'? If so, it can't be connected to any receptor term (e.g. it can't have 'positively_regulates EGF-activated receptor activity, because that's not the same thing).

If we have 'EGFR agonist' which positively_regulates 'EGF-activated receptor activity, it can ONLY be used to annotate EGF. Which seems restrictive and not useful.

Or should we capture this information in column 16 and forget about the links within the ontology?



RECEPTOR BINDING

When we say 'epidermal growth factor receptor binding ; GO:0005154' do we mean:

  1. Binding to the gene product 'Egfr'.
  2. Binding to a receptor that is activated by EGF

You can't bind to an activity. But you can bind to a GP that has an activity.



SIGNAL GENERATION

  • Q: Is signal generation THE START OF signaling or UPSTREAM of signaling?
    • Need to decide, for placement of GO:0003001, which says that generation of the signal is involved in signaling. This contradicts the current definition of signaling which begins with an active signal.
    • Is biosynthesis of the signal (e.g. translation/sphingolipid biosynthesis/light generation) really part of signaling?
generation of a signal involved in cell-cell signaling ; GO:0003001
This process begins with the initial formation of the signal and ends with the mature form and placement of the signal. 
signaling ; GO:0023052
This process begins with an active signal and ends when a cellular response has been triggered.



ACTIVATED VERSUS MEDIATED

  • Need to standardise term names to 'activated' OR 'mediated'. E.g.:
    • collagen-activated signaling pathway ; GO:0038065
    • cytokine-mediated signaling pathway ; GO:0019221


CARBOHYDRATE-MEDIATED SIGNALING

Q: What do we mean by 'carbohydrate mediated signaling ; GO:0009756'. Is carbohydrate a ligand for a receptor?



LIGAND RECEPTOR SIGNALING PATHWAYS

  • It's confusing to have 'ligand receptor signaling pathways'
    • gurken receptor signaling pathway
    • wnt receptor signaling pathway
  • We could remove 'receptor' from the names:
    • gurken signaling pathway (or gurken-activated signaling pathway)
    • Wnt signaling pathway

This may mess up the growth factor receptor signaling pathways. And GPCRs. Is it: EGF-signaling pathway or 'EGFR signaling pathway'?



TOO BROAD FOR MANUAL ANNOTATION

Should these be made too broad for manual annotation?

signal transduction ; GO:0007165 signal transducer activity ; GO:0004871


LIGAND-GATED ION CHANNELS

QUESTION: Should these have parentage in the 'receptor' node of GO?

[[3]]




Minutes

Alot of discussion about the intracellular signaling cassettes, and where they should stop and start. Suggested by David H, that PI3K signaling begins WITH PI3K. But a lot of annotations have been using the term more broadly to mean anything that signals THROUGH PI3K (including ligands, receptors, upstream activators and downstream effectors).

AI: Becky to have a play with the ontology and broaden PI3K signaling to mean anything that signals through PI3K (will need to decide whether to move out from under intracellular signal transduction). Then create a separate module for PI3K signaling which will have a HAS_PART link to the whole pathway.


Chris presented a demo of how this links to LEGO. For more details, see: https://docs.google.com/document/d/1TV8Eb9sSvFY-weVZaIfzCxF1qbnmkUaiUhTm9Bs3gRE/edit#


Return to Signaling Main Page [[4]]