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Diagram courtesy of NEB.
Daniel R. Caffrey, Luke A.J. O'Neill, Denis C. Shields
Abstract. The MAP–kinase pathways are intra-cellular signaling modules that are likely to exist in all eukaryotes. We provide an evolutionary model for these signaling pathways by focusing on the gene duplications that have occurred since the divergence of animals from yeast. Construction of evolutionary trees with confidence assessed by bootstrap clearly show that the mammalian JNK and p38 pathways arose from an ancestral hyper–osmolarity pathway after the split from yeast and before the split from C. elegans.These co-duplications of interacting proteins at the MAPK and MEK levels have since evolved towards substrate specificity, thus giving distinct pathways. Mammalian duplications since the split from C. elegans are often associated with divergent tissue distribution but do not appear to confer detectable substrate specificity. The yeast kinase cascades have undergone similar fundamental functional changes since the split from mammals, with duplications giving rise to central signaling components of the filamentous and hypo-osmolarity pathways. Experimentally defined cross-talk between yeast pheromone and hyper-osmolarity pathways is mirrored with a corresponding cross-talk in mammalian pathways, suggesting the existence of an ancient orthologous cross-talk; our analysis of gene duplications at all levels of the cascade is consistent with this model, but does not always provide significant bootstrap support. Our data also provides insights at different levels of the cascade where conflicting experimental evidence exists.
medline abstract.
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Diagram courtesy of NEB.
Click on relevent link to see more information on sequences.
Note: I have tried to include the multiple acronyms for each protein.
Please let me know if I have ommited any of the widely used names.
The MAPK sequences.
The MEK sequences.
The MEKK sequences.
The STE20-PAK sequences.
Excluded sequences.
Interesting Sequences not included in the analysis.
Click on the relevent link, then cut and paste into an editor or wordproccesor. To view files in exotic word processors you should change the text to courier style and decrease the font to size 6 or 8. TO MANIPULATE OR VIEW THE ALIGNMENTS WE RECOMMEND THAT YOU USE CLUSTALW1.7 OR CLUSTALX AS OLDER VERSIONS MAY NOT HANDLE THE FILES WELL.
Name Last modified Size Description
mapk.aln 09-Nov-98 15:53 40.3K mek.aln 09-Nov-98 16:28 25.6K mekk.aln 09-Nov-98 16:28 19K ste20-pak.aln 09-Nov-98 16:28 30.6K all.aln 09-Nov-98 16:28 187.6K
Click on the relevent link, then cut and paste into an editor or wordproccesor. The trees can be viewed with njplot. NOTE: The bootstrap values are for 1000 replicates (the paper rounds these off to a percentage).
mapk.phb 21-Nov-98 17:48 1.8K
GIFS from paper
Figure 1 Schematic Diagram Figure 2 MAPK Tree Figure 3 MEK Tree Figure 4 MEKK Tree Figure 5 STE20-PAK Tree
Schematic Diagrams
Diagram 1 from NEB. Diagram 2 from Woodget lab. Diagram 3 from Davis lab. Diagram 4 from Cohen lab.
Email:dcaffrey@rcsi.ie Home page.