Cleaning up MAPKKK cascade: Difference between revisions

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==<font color="blue">Defining the start and end of the MAPKKK cascade</font>==
[[Category:Signaling]]
==<font color="navy">BACKGROUND</font>==


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


*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:
==<font color="navy">STILL TO DO</font>==
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 ????


<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?
SourceForge item from Val sorting out the different types of MAPK cascades:
https://sourceforge.net/p/geneontology/ontology-requests/10384/


--Ruth says no


<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


---------------------
==<font color="navy">REDEFINING 'MAPK CASCADE'</font><font color="green">DONE</font>==


Renamed (end 2011):
MAPKKK cascade ; GO:0000165
to
MAPK cascade ; GO:0000165


==<font color="magenta">Term obsoletions</font>==
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.


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:


<pre>


activation of MAPK activity ; GO:0000187
==<font color="navy">PROCESS-FUNCTION RELATIONSHIPS'</font><font color="green">DONE</font>==
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
* Created P/F links to connect the MAPK(n) activities to the downstream cascade components they activate (end 2011):
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
E.g:
activation of JNKKK activity ; GO:0042655
MAPK cascade
activation of MAPKKK activity involved in cell wall biogenesis ; GO:0000197
--[partof]MAP kinase activity (new relationship)
activation of MAPKKK activity involved in conjugation with cellular fusion ; GO:0071510
----[pos_reg]positive regulation of MAP kinase activity
activation of MAPKKK activity involved in innate immune response ; GO:0035422
------[isa]activation of MAPK activity
activation of MAPKKK activity involved in osmosensory signaling pathway ; GO:0000167
--------[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


inactivation of MAPK activity ;GO:0000188
* 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.
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
==<font color="navy">MAPK FUNCTION TERMS</font>==
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'


* Need to sort out the distinction between MAPK/SAPK/JNK activities. Currently (May 2012):


<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).
MAP kinase activity ; GO:0004707
--[isa]SAP kinase activity ; GO:0016909
----[isa]JUN kinase activity ; GO:0004705


</pre>


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:
<pre>
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
</pre>
<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>


---------------------
---------------------


==<font color="Navy">NEW REGULATION TERMS</font>==
==Relevant SourceForge Items==


For the activation/inactivation terms:
* The start and end of the MAPKKK cascade: https://sourceforge.net/tracker/?func=detail&aid=3085150&group_id=36855&atid=440764
<pre>
* Cleaning up MAPKs: https://sourceforge.net/tracker/?func=detail&aid=1996264&group_id=36855&atid=440764 DONE
activation of MAPKKK activity ; GO:0000185 is not connected (via a REGULATES relationship) to the function term MAP kinase kinase kinase activity ; GO:0004709
* SAPKs/JNKs: https://sourceforge.net/tracker/?func=detail&aid=1000127&group_id=36855&atid=440764
activation of MAPKK activity ; GO:0000186 is not connected (via a REGULATES relationship) to the function term MAP kinase kinase activity ; GO:0004708
* MAPKs: https://sourceforge.net/p/geneontology/ontology-requests/10384/
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)
 
</pre>
 
---------------------
 
==<font color="green">Add in process-function links for the enzymes that are part of the MAPKKK cascade</font>==
 
The MAPKKKkkkkk function terms should be connected to the MAPKKK cascade ; GO:0000165 terms. E.g.:
 
<pre>
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.
 
</pre>
 
<font color="red">*Q5:Do we want to add in links to the 'positive regulation of activity terms</font>. E.g.
 
<pre>
 
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.
 
</pre>
 
---------------------
 
==<font color="red">Standardise the term names</font>==
 
*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.
 
 
---------------------

Latest revision as of 17:54, 22 April 2014

BACKGROUND

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.


STILL TO DO

SourceForge item from Val sorting out the different types of MAPK cascades: https://sourceforge.net/p/geneontology/ontology-requests/10384/


REDEFINING 'MAPK CASCADE'DONE

Renamed (end 2011): 

MAPKKK cascade ; GO:0000165
to
MAPK cascade ; GO:0000165

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.


PROCESS-FUNCTION RELATIONSHIPS'DONE

  • Created P/F links to connect the MAPK(n) activities to the downstream cascade components they activate (end 2011):
E.g:
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
  • 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.


MAPK FUNCTION TERMS

  • Need to sort out the distinction between MAPK/SAPK/JNK activities. Currently (May 2012):
MAP kinase activity ; GO:0004707
--[isa]SAP kinase activity ; GO:0016909
----[isa]JUN kinase activity ; GO:0004705


Relevant SourceForge Items

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