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 ????
*Q1: 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
*Q2: 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 obsoletions
Ruth and Suzi pointed out that the following terms seem to describe a single-step function rather than a process. The definitions are also a bit confusing:
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) E.g term: activation of MAPK activity ; GO:0000187 Def:The initiation of the activity of the inactive enzyme MAP kinase by phosphorylation by a MAPKK. This term is describing the function: 'MAP kinase kinase activity ; GO:0004708'
*Q3: Is inactivation of MAPKKK, MAPKK and MAPK really part of the MAPKKK cascade? (If they are kept, I would like to move them to the negative regulation of MAPKKK cascade term).
Proposal: we could obsolete all of the above, and add in function-process links to the MAPKKKKkkk function terms instead.
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
*Q4: Is there ever a case where you'd want to annotate to one of the child terms rather than the 'MAPKKK cascade involved in x' parent??
*Q5: Is there ever a case where you'd use one of the activation terms to annotate a NON-MAPKKkkkkkkk?
NEW REGULATION TERMS
For the activation/inactivation terms:
activation of MAPKKK activity ; GO:0000185 is not connected (via a REGULATES relationship) to the function term MAP kinase kinase kinase activity ; GO:0004709 activation of MAPKK activity ; GO:0000186 is not connected (via a REGULATES relationship) to the function term MAP kinase kinase activity ; GO:0004708 activation of MAPK activity IS connected (via a REGULATES relationship) to the function term MAP kinase activity; 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 If GO:0000187 is obsoleted, the 'regulation of MAP kinase activity' terms would remain. 'activation of MAPK activity can be added as a narrow_synonym for GO:0043406'. I can add in 'regulation of MAPKK activity' and 'regulation of MAPKKK activity' terms to match: 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
The MAPKKKkkkkk function terms should be connected to the MAPKKK cascade ; GO:0000165 terms. E.g.:
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.
*Q6:Do we want to add in links to the 'positive regulation of activity terms. E.g.
positive regulation of MAPKKK activity ; GO:NEW --<MAP kinase kinase kinase kinase activity ; GO:0008349 positive regulation of MAPKK activity ; GO:NEW --<MAP kinase kinase kinase activity ; GO:0004709 positive regulation of MAPK activity ; GO:0043406 --<MAP kinase kinase activity ; GO:0004708 This means that the MAPKKkkkkkkkk activities would be both part of the cascade, and part of the regulation of the cascade, so we might not want to go this route.
Standardise the term 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.
Related SourceForge Items
- The start and end of the MAPKKK cascade: https://sourceforge.net/tracker/?func=detail&aid=3085150&group_id=36855&atid=440764