Cleaning up MAPKKK cascade

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Defining the start and end of the MAPKKK cascade

We need to define the start and end points of 'MAPKKK cascade ; GO:0000165' because the definition is out of sync with its children:

  • Current definition: A cascade of at least three protein kinase activities culminating in the phosphorylation and activation of a MAP kinase. MAPKKK cascades lie downstream of numerous signaling pathways.

Suggested change: The sequential phosphorylation and activation of at least three protein kinases. The MAPKKK cascade begins with activation of a MAP kinase kinase kinase (MAPKKK) and ends with ????

  • Q: does the MAPKKK cascade include MAPK activity (ie phosphorylation of downstream substrates by MAPK) or does it end at activation of MAPK?

--Ruth says no

  • Q: does the MAPKKK cascade include nuclear translocation of MAPK? (GO:0000189 is a part_of child at the moment). NB: Not all MAPKs translocate to the nucleus as some targets are cytoplasmic)

Term obsoletion

With process-function links, Ruth and Suzi pointed out that the following terms appear redundant. The definitions are also pretty terrible and open to misinterpretation.


activation of MAPK activity ;GO:0000187
activation of JUN kinase activity ; GO:0007257
activation of MAPK activity by adrenergic receptor signaling pathway ; GO:0071883
activation of MAPK activity involved in cell wall biogenesis ; GO:0000199
activation of MAPK activity involved in conjugation with cellular fusion ; GO:0071508
activation of MAPK activity involved in innate immune response ; GO:0035419
activation of MAPK activity involved in osmosensory signaling pathway ; GO:0000169

activation of MAPKK activity ; GO:0000186
activation of JNKK activity ; GO:0007256
activation of MAPKK activity involved in cell wall biogenesis ; GO:0000198
activation of MAPKK activity involved in conjugation with cellular fusion ; GO:0071509
activation of MAPKK activity involved in innate immune response ; GO:0035421
activation of MAPKK activity involved in osmosensory signaling pathway ; GO:0000168

activation of MAPKKK activity ; GO:0000185
activation of JNKKK activity ; GO:0042655
activation of MAPKKK activity involved in cell wall biogenesis ; GO:0000197
activation of MAPKKK activity involved in conjugation with cellular fusion ; GO:0071510
activation of MAPKKK activity involved in innate immune response ; GO:0035422
activation of MAPKKK activity involved in osmosensory signaling pathway ; GO:0000167

inactivation of MAPK activity ;GO:0000188
inactivation of MAPK activity involved in cell wall biogenesis ; GO:0000200
inactivation of MAPK activity involved in conjugation with cellular fusion ; GO:0071511
inactivation of MAPK activity involved in innate immune response ; GO:0035423
inactivation of MAPK activity involved in osmosensory signaling pathway ; GO:0000173

inactivation of MAPKK activity ; GO:0051389 (NO CHILDREN)
inactivation of MAPKKK activity ; GO:0051390 (NO CHILDREN)
(I don't think inactivation of the enzymes is part of the cascade).

We could obsolete all of the above.

For the 'involved in' terms, annotations could be transferred to the parent terms:

MAPKKK cascade involved in cell wall biogenesis ; GO:0000196
MAPKKK cascade involved in conjugation with cellular fusion ; GO:0071507
MAPKKK cascade involved in innate immune response ; GO:0035420
MAPKKK cascade involved in osmosensory signaling pathway ; GO:0000161

For the activation/inactivation terms:

activation of MAPKKK activity ; GO:0000185 is not connected to the function:GO:0004709
activation of MAPKK activity ; GO:0000186 is not connected to the function:GO:0004708
activation of MAPK activity IS connected to the function:GO:0000187:

MAP kinase activity ; GO:0004707
--[R]regulation of MAP kinase activity ; GO:0043405
----[i]positive regulation of MAP kinase activity ; GO:0043406
------[i]activation of MAPK activity ; GO:0000187

With obsoletion of GO:0000187, the 'regulation of MAP kinase activity' terms would remain. 'activation of MAPK activity can be added as a synonym for GO:0043406'.

I can add in 'regulation of MAPKK activity' and 'regulation of MAPKKK  activity' terms to match. I believe this would be more consistent with the rest of GO:

MAPKK activity ; GO:0004708
--[R]regulation of MAPKK activity ; GO:NEW1
----[i]positive regulation of MAPKK activity ; GO:NEW2
----[i]negative regulation of MAPKK activity ; GO:NEW3

MAPKKK activity ; GO:0004709
--[R]regulation of MAPKKK activity ; GO:NEW4
----[i]positive regulation of MAPKKK activity ; GO:NEW5
----[i]negative regulation of MAPKKK activity ; GO:NEW6

regulation of MAPKKK cascade ; GO:0043408
--%regulation of MAP kinase activity ; GO:0043405 (new relationship)
--%regulation of MAPKK activity ; GO:NEW1
--%regulation of MAPKKK activity ; GO:NEW4

(with the usual intersections and relationships)


Add in process-function links for the enzymes that are part of the MAPKKK cascade

Suggested function terms:

MAPKKK cascade ; GO:0000165
--<MAP kinase kinase kinase kinase activity ; GO:0008349
--<MAP kinase kinase kinase activity ; GO:0004709
--<MAP kinase kinase activity ; GO:0004708
--<MAP kinase activity ; GO:0004707 * 

* depends on where we say the cascade ends.

Standardise the tern names

  • The process terms use the abbreviations: MAPK, MAPKK, MAPKKK
  • The function names spell out the kinases: MAP kinase, MAP kinase kinase etc

Since most people I think would search on 'MAPK' not 'MAP kinase', I've like to shorten all the function names to match process, keeping the full names as synonyms.




Stress-activated protein kinase signaling cascade


Current tree:
stress-activated protein kinase signaling cascade ; GO:0031098
--%JNK cascade ; GO:0007254
--%stress-activated MAPK cascade ; GO:0051403

MAPKKK cascade
--%JNK cascade ; GO:0007254
--%stress-activated MAPK cascade ; GO:0051403

GO:0007254 should be made a child not a sibling of GO:0051403, based on this. I'll come back to GO:0031098 to see what's meant by this term. One (or a few) things at a time.