Intracellular signal transduction

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WHAT NEEDS TO BE DONE / BACKGROUND

Intracellular signal transduction needs some attention but this is a good case-study for the LEGO model.

One of the key problems for the intracellular signaling modules is defining where the intracellular signaling starts and stops.

The most recent (November 2013) proposal for intracellular signaling is to have signaling modules which require 2 OR MORE DEFINED COMPONENTS. E.g. PI3K-AKT signaling module. These module terms would be in addition to general 'PI3K signaling' and 'AKT signaling' terms. For more details on this proposal see [2]. A mock-up of how the modules could look is shown below

Becky emailed this proposal to Mike T, Andrew W. and Andrew C-A. Andrew C-A responded but wasn't sure the solution would fix the confusion.

Intracellular Signaling Examples

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

Connecting Intracellular Cascades To Cell Surface Receptors

For the problems of connecting the intracellular signaling cascades with the cell surface receptors above them, see slides 26-32 of the overview from the LA GOC meeting, May 2011.

From the GO signaling workshop and the LA 2011 GO meeting, it was agreed that 'VIA' (and HAS_PART relationships) was the most appropriate syntax for these terms.

For the current discussions on representing the regulatory nature of signaling pathways, see [3]

EDITS: SEPTEMBER 8th 2011

OBSOLETED:
intracellular signal transduction involved in cell surface receptor linked signaling ; GO:0035557
phosphatidylinositol 3-kinase cascade involved in insulin receptor signaling ; GO:0035558
MAPKKK cascade involved in epidermal growth factor receptor signaling ; GO:0035559

Created new Replacement Terms:

id: GO:0038028
name: insulin receptor signaling pathway via phosphatidylinositol 3-kinase cascade
namespace: biological_process
def: "The series of molecular signals generated as a consequence of the insulin receptor binding to its physiological ligand, where the signal is passed on via the   phosphatidylinositol 3-kinase cascade." [GOC:bf, GOC:signaling, PMID:19322168, PMID:20696212]
synonym: "insulin receptor signaling pathway via PI3K cascade" EXACT [GOC:bf]
synonym: "insulin receptor signaling via PI3K" EXACT [GOC:bf]
is_a: GO:0008286 ! insulin receptor signaling pathway
relationship: has_part GO:0014065 ! phosphatidylinositol 3-kinase cascade

id: GO:0038029
name: epidermal growth factor receptor signaling pathway via MAPKKK cascade
namespace: biological_process
def: "The series of molecular signals generated as a consequence of an epidermal growth factor receptor binding to one of its physiological ligands, where the signal is  passed on via the MAPKKK cascade." [GOC:bf, GOC:signaling, PMID:21167805]
synonym: "EGFR signaling pathway via MAPKKK cascade" EXACT [GOC:bf]
synonym: "EGFR signaling via MAPKKK cascade" EXACT [GOC:bf]
synonym: "EGFR/MAPK signaling" EXACT [GOC:bf]
synonym: "epidermal growth factor receptor signalling pathway via MAPKKK cascade" EXACT [GOC:bf]
is_a: GO:0007173 ! epidermal growth factor receptor signaling pathway
relationship: has_part GO:0000165 ! MAPKKK cascade

For SF:3023417, created:
non-canonical Wnt receptor signaling pathway via MAPKKK cascade ; GO:0038030
non-canonical Wnt receptor signaling pathway via JNK cascade ; GO:0038031

Related SourceForge Items

PI3K/AKT signaling: https://sourceforge.net/tracker/?func=detail&aid=3008502&group_id=36855&atid=440764
Wnt signaling via JNK: https://sourceforge.net/tracker/?func=detail&aid=3023417&group_id=36855&atid=440764 DONE
Regulation of Wnt signaling by Hippo signaling: https://sourceforge.net/tracker/?func=detail&aid=3032564&group_id=36855&atid=440764
Opoid receptor signaling: https://sourceforge.net/tracker/?func=detail&aid=3196318&group_id=36855&atid=440764
Activation of phospholipase C by GPCR signaling: https://sourceforge.net/tracker/?func=detail&aid=3117691&group_id=36855&atid=440764

Naming The Cascades

For the problems of connecting the intracellular signaling cascades with the cell surface receptors above them, see slide 32 of the overview from the LA GOC meeting, May 2011.

IN SUMMARY:

There was a concern that ‘cascade’ implied amplification of a signal, so these were renamed at the end of 2013.
The SWG and experts discussed various options including 'cascade, cassette, module'.

In November 2013, the 'cascade' wording was removed from intracellular signaling terms that did NOT amplify a signal. 'x signal transduction' exact synonyms were added to all the intracellular signaling terms.

Intracellular Signaling: Where does it start and stop?

Intracellular signaling units can be split into those that are a group of proteins:

MAPKKK cascade
JNK cascade
Hippo signal transduction

and those that are really just one mediator/protein:

PI3K
PKB (aka AKT) (NB: PI3K and AKT NORMALLY (but not always) signal together so we need to look at how we can connect them.
TOR
Ca++ signaling
Activation/inhibition of adenylate cyclase in GPCR signaling

For those that are just one mediator, it's harder to define a start and stop point. Where, for example, does PI3K signal transduction begin and end?

The cascades were discussed at the call on 25th November 2013: [4]. On this call it was suggested that:

-PI3K signaling would refer to any intracellular signal transduction that goes VIA PI3K. E.g. events above and below PI3K -We would create signaling cassettes consisting of at least 2 signaling components, and define a start and stop for these cassettes. E.g. PI3K-AKT-TOR cassette.

Becky emailed this proposal to Prof. Mike Tyers, Andrew Winter and Andrew Chatyr-Aryamontri. We need to make sure this we could still capture a GP that regulates e.g. PKB activity.