Cleaning up MAPKKK cascade: Difference between revisions

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[[Category:Signaling]]
==<font color="navy">BACKGROUND</font>==


==<font color="blue">Defining the start and end of the MAPKKK cascade</font>==
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.


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.
==<font color="navy">STILL TO DO</font>==


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


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


---------------------
Renamed (end 2011):
 
MAPKKK cascade ; GO:0000165
==<font color="magenta">Term obsoletion</font>==
to
 
MAPK cascade ; GO:0000165
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.
 
<pre>
 
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).


</pre>
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.


We could obsolete all of the above.


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>


*Q: 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 color="navy">PROCESS-FUNCTION RELATIONSHIPS'</font><font color="green">DONE</font>==
---------------------


==<font color="Navy">NEW REGULATION TERMS</font>==
* Created P/F links to connect the MAPK(n) activities to the downstream cascade components they activate (end 2011):


For the activation/inactivation terms:
E.g:
<pre>
MAPK cascade
activation of MAPKKK activity ; GO:0000185 is not connected to the function term MAP kinase kinase kinase activity ; GO:0004709
--[partof]MAP kinase activity (new relationship)
activation of MAPKK activity ; GO:0000186 is not connected to the function term MAP kinase kinase activity ; GO:0004708
----[pos_reg]positive regulation of MAP kinase activity
activation of MAPK activity IS connected to the function term MAP kinase activity; GO:0000187:
------[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


MAP kinase activity ; GO:0004707
* 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 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
==<font color="navy">MAPK FUNCTION TERMS</font>==
--[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
* Need to sort out the distinction between MAPK/SAPK/JNK activities. Currently (May 2012):
--[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
MAP kinase activity ; GO:0004707
--%regulation of MAP kinase activity ; GO:0043405 (new relationship)
--[isa]SAP kinase activity ; GO:0016909
--%regulation of MAPKK activity ; GO:NEW1
----[isa]JUN kinase activity ; GO:0004705
--%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>==
==Relevant SourceForge Items==


Suggested function 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
MAPKKK cascade ; GO:0000165
* SAPKs/JNKs: https://sourceforge.net/tracker/?func=detail&aid=1000127&group_id=36855&atid=440764
--<MAP kinase kinase kinase kinase activity ; GO:0008349
* MAPKs: https://sourceforge.net/p/geneontology/ontology-requests/10384/
--<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>
 
*Q:Do we want to add in links to the 'positive regulation of activity terms'. 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 terms so we might not want to go this route.
 
</pre>
 
---------------------
 
==<font color="red">Standardise the tern 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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