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| ==<font color="blue">Defining the start and end of the MAPKKK cascade</font>==
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| We need to define the start and end points of 'MAPKKK cascade ; GO:0000165' because the definition is out of sync with its children:
| | ==<font color="blue">BACKGROUND</font>== |
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| *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.
| | MAPK cascades lie downstream of many cell surface receptors and cooperate in transmitting various extracellular signals to the nucleus. One way by which the specificity of each cascade is regulated is through the existence of several distinct components in each tier of the different cascades. The cascades are typically named according to the component in the MAPK tier. |
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| Suggested change:
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| 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 ????
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| <font color="red">*Q1: does the MAPKKK cascade include MAPK activity?</font> (ie phosphorylation of downstream substrates by MAPK) or does it end at activation of MAPK? | | ==<font color="blue">REDEFINING 'MAPK CASCADE'</font><font color="green">DONE</font>== |
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| --Ruth says no
| | Renamed: |
| | MAPKKK cascade ; GO:0000165 |
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| | MAPK cascade ; GO:0000165 |
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| <font color="red">*Q2: does the MAPKKK cascade include nuclear translocation of MAPK?</font> (GO:0000189 is a part_of child at the moment). NB: Not all MAPKs translocate to the nucleus as some targets are cytoplasmic
| | And redefined as a cascade containing at least MAPKKK, MAPKK and MAPK based on PMID 20811974 (from Paul Thomas's regulation proposal: |
| | http://gocwiki.geneontology.org/index.php/Ontology_meeting_2012-01-19. Also redefined the child terms accordingly. |
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| ---------------------
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| ==<font color="magenta">Term obsoletions</font>==
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| 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:
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| <pre>
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| activation of MAPK activity ; GO:0000187
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| activation of JUN kinase activity ; GO:0007257
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| activation of MAPK activity by adrenergic receptor signaling pathway ; GO:0071883
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| activation of MAPK activity involved in cell wall biogenesis ; GO:0000199
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| activation of MAPK activity involved in conjugation with cellular fusion ; GO:0071508
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| activation of MAPK activity involved in innate immune response ; GO:0035419
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| activation of MAPK activity involved in osmosensory signaling pathway ; GO:0000169
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| activation of MAPKK activity ; GO:0000186
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| activation of JNKK activity ; GO:0007256
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| activation of MAPKK activity involved in cell wall biogenesis ; GO:0000198
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| activation of MAPKK activity involved in conjugation with cellular fusion ; GO:0071509
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| activation of MAPKK activity involved in innate immune response ; GO:0035421
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| activation of MAPKK activity involved in osmosensory signaling pathway ; GO:0000168
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| activation of MAPKKK activity ; GO:0000185
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| activation of JNKKK activity ; GO:0042655
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| activation of MAPKKK activity involved in cell wall biogenesis ; GO:0000197
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| activation of MAPKKK activity involved in conjugation with cellular fusion ; GO:0071510
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| activation of MAPKKK activity involved in innate immune response ; GO:0035422
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| activation of MAPKKK activity involved in osmosensory signaling pathway ; GO:0000167
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| inactivation of MAPK activity ;GO:0000188
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| inactivation of MAPK activity involved in cell wall biogenesis ; GO:0000200
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| inactivation of MAPK activity involved in conjugation with cellular fusion ; GO:0071511
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| inactivation of MAPK activity involved in innate immune response ; GO:0035423
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| inactivation of MAPK activity involved in osmosensory signaling pathway ; GO:0000173
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| inactivation of MAPKK activity ; GO:0051389 (NO CHILDREN)
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| inactivation of MAPKKK activity ; GO:0051390 (NO CHILDREN)
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| E.g
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| term: activation of MAPK activity ; GO:0000187
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| Def:The initiation of the activity of the inactive enzyme MAP kinase by phosphorylation by a MAPKK.
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| This term is describing the function: 'MAP kinase kinase activity ; GO:0004708'
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| </pre>
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| <font color="red">*Q3: Is inactivation of MAPKKK, MAPKK and MAPK really part of the MAPKKK cascade?</font> (If they are kept, I would like to move them to the negative regulation of MAPKKK cascade term).
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| Proposal: we could obsolete all of the above, and add in function-process links to the MAPKKKKkkk function terms instead.
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| For the 'involved in' terms, annotations could be transferred to the parent terms:
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| <pre>
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| MAPKKK cascade involved in cell wall biogenesis ; GO:0000196
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| MAPKKK cascade involved in conjugation with cellular fusion ; GO:0071507
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| MAPKKK cascade involved in innate immune response ; GO:0035420
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| MAPKKK cascade involved in osmosensory signaling pathway ; GO:0000161
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| </pre>
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| <font color="red">*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??</font>
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| <font color="red">*Q5: Is there ever a case where you'd use one of the activation terms to annotate a NON-MAPKKkkkkkkk?</font>
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| ==<font color="Navy">NEW REGULATION TERMS</font>==
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| For the activation/inactivation terms:
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| <pre>
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| activation of MAPKKK activity ; GO:0000185 is not connected (via a REGULATES relationship) to the function term MAP kinase kinase kinase activity ; GO:0004709
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| activation of MAPKK activity ; GO:0000186 is not connected (via a REGULATES relationship) to the function term MAP kinase kinase activity ; GO:0004708
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| activation of MAPK activity IS connected (via a REGULATES relationship) to the function term MAP kinase activity; GO:0000187:
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| MAP kinase activity ; GO:0004707
| | ==<font color="blue">PROCESS-FUNCTION RELATIONSHIPS'</font><font color="green">DONE</font>== |
| --[R]regulation of MAP kinase activity ; GO:0043405 | |
| ----[i]positive regulation of MAP kinase activity ; GO:0043406
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| ------[i]activation of MAPK activity ; GO:0000187
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| 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'.
| | * Created P/F links to connect the MAPK(n) activities to the downstream cascade components they activate: |
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| I can add in 'regulation of MAPKK activity' and 'regulation of MAPKKK activity' terms to match:
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| | MAPK cascade |
| | --[partof]MAP kinase activity (new relationship) |
| | ----[pos_reg]positive regulation of MAP kinase activity |
| | ------[isa]activation of MAPK activity |
| | --------[partof]MAP kinase kinase activity (new relationship) |
| | ----------[pos_reg]positive regulation of MAP kinase kinase activity |
| | ------------[isa] activation of MAP kinase kinase activity |
| | --------------[partof]MAP kinase kinase kinase activity (new relationship) |
| | etc etc |
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| MAPKK activity ; GO:0004708
| | * Note that this is a temporary solution because we can't yet say in GO that MF regulates MF. When we can, we will able to obsolete the redundant regulation process terms in this node. |
| --[R]regulation of MAPKK activity ; GO:NEW1
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| ----[i]positive regulation of MAPKK activity ; GO:NEW2
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| ----[i]negative regulation of MAPKK activity ; GO:NEW3
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| MAPKKK activity ; GO:0004709
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| --[R]regulation of MAPKKK activity ; GO:NEW4
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| ----[i]positive regulation of MAPKKK activity ; GO:NEW5
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| ----[i]negative regulation of MAPKKK activity ; GO:NEW6
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| regulation of MAPKKK cascade ; GO:0043408
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| --%regulation of MAP kinase activity ; GO:0043405 (new relationship)
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| --%regulation of MAPKK activity ; GO:NEW1
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| --%regulation of MAPKKK activity ; GO:NEW4
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| (with the usual intersections and relationships)
| | ==<font color="blue">MAPK FUNCTION TERMS</font>== |
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| </pre>
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| ---------------------
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| ==<font color="green">Add in process-function links for the enzymes that are part of the MAPKKK cascade</font>== | |
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| The MAPKKKkkkkk function terms should be connected to the MAPKKK cascade ; GO:0000165 terms. E.g.:
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| <pre>
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| MAPKKK cascade ; GO:0000165
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| --<MAP kinase kinase kinase kinase activity ; GO:0008349
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| --<MAP kinase kinase kinase activity ; GO:0004709
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| --<MAP kinase kinase activity ; GO:0004708
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| --<MAP kinase activity ; GO:0004707 !
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| ! depends on where we say the cascade ends.
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| </pre>
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| <font color="red">*Q6:Do we want to add in links to the 'positive regulation of activity terms</font>. E.g.
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| <pre>
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| positive regulation of MAPKKK activity ; GO:NEW
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| --<MAP kinase kinase kinase kinase activity ; GO:0008349
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| positive regulation of MAPKK activity ; GO:NEW
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| --<MAP kinase kinase kinase activity ; GO:0004709
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| positive regulation of MAPK activity ; GO:0043406
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| --<MAP kinase kinase activity ; GO:0004708
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| 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.
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| </pre>
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| ==<font color="red">Standardise the term names</font>==
| | * Need to sort out the distinction between MAPK/SAPK/JNK activities. Currently (May 2012): |
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| *The process terms use the abbreviations: MAPK, MAPKK, MAPKKK
| | MAP kinase activity ; GO:0004707 |
| *The function names spell out the kinases: MAP kinase, MAP kinase kinase etc
| | --[isa]SAP kinase activity ; GO:0016909 |
| | ----[isa]JUN kinase activity ; GO:0004705 |
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| 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.
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| --------------------- | | --------------------- |
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| ==Related SourceForge Items== | | ==Relevant SourceForge Items== |
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| * The start and end of the MAPKKK cascade: https://sourceforge.net/tracker/?func=detail&aid=3085150&group_id=36855&atid=440764 | | * The start and end of the MAPKKK cascade: https://sourceforge.net/tracker/?func=detail&aid=3085150&group_id=36855&atid=440764 |
| * Cleaning up MAPKs: https://sourceforge.net/tracker/?func=detail&aid=1996264&group_id=36855&atid=440764 DONE | | * Cleaning up MAPKs: https://sourceforge.net/tracker/?func=detail&aid=1996264&group_id=36855&atid=440764 DONE |
| | * SAPKs/JNKs: https://sourceforge.net/tracker/?func=detail&aid=1000127&group_id=36855&atid=440764 |