WNKs: atypical protein kinases with pleiotropic actions

The evidence used to generate this figure is discussed in [section III.B.]. The MAPK pathway is activated by growth factors and both environmental and intracellular stress, resulting in proliferative or stress responses through regulation of gene transcription. The ERK pathway is stimulated primarily by growth factors and tumor promoters, whereas the JNK and p38 MAPK pathways are activated by pro-inflammatory cytokines and environmental stress, including hyperosmotic stress. Members of the WNK kinase family influence MAP kinase signaling pathways as shown. EGF receptor activation stimulates WNK1 which in turn activates of ERK5. Stimulation of ERK5 by WNK1 requires MEK5 and MEKK2/3 activity, and WNK1 physically interacted MEKK2/3. WNK2 inhibits ERK1/2 activation by controlling the balance of upstream regulators of PAK1 activity, RhoA and RacI. WNK4 stimulates both ERK1/2 and p38 MAPKs in response to both hypertonic stress and stimulation with EGF. ? indicate where intermediates in the signaling pathways are unknown.

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The WNKs: atypical protein kinases with pleiotropic actions. () James A. McCormick, et al. Physiol Rev. ;91(1):177-219. Figure: F11. All organisms Arabidopsis thaliana Gallus gallus Caenorhabditis elegans Mus musculus Rattus norvegicus Homo sapiens Xenopus tropicalis Drosophila melanogaster Rattus rattus Danio rerio Xenopus laevis

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