Cleaning up MAPKKK cascade
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.