Cascades

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CONNECTING INTRACELLULAR SIGNALING 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.

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.
• The SWG and experts discussed various options including 'cascade, cassette, module'.
• It was decided to stick with 'cascade' in GO, and making it clear in the definitions that amplification of a signal was not required.

CASCADE PROBLEMS STILL TO ADDRESS

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

• MAPKKK cascade
• JNK cascade
• Hippo cascade

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 the PI3K cascade begin and end? For these, it may be easier to rename them to 'PI3K signaling'. If we keep it as an instance of intracellular signal transduction, it can be defined as any signaling event within the cell where PI3K passes the signal on.