Two Dictyostelium tyrosine kinase-like kinases function in parallel, stress-induced STAT activation pathways.
Bottom Line: The signaling pathways that activate Pyk2 and Pyk3 are only partially overlapping, and there may be a structural basis for this difference because Pyk3 contains both a TKL domain and a pseudokinase domain.The latter functions, like the JH2 domain of metazoan JAKs, as a negative regulator of the kinase domain.The fact that two differently regulated kinases catalyze the same phosphorylation event may facilitate specific targeting because under stress, Pyk3 and Pyk2 accumulate in different parts of the cell; Pyk3 moves from the cytosol to the cortex, whereas Pyk2 accumulates in cytosolic granules that colocalize with PTP3.
Affiliation: College of Life Sciences, Welcome Trust Biocentre, University of Dundee, Dundee DD1 5EH, United Kingdom.Show MeSH
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Mentions: The developmental phenotype of the three mutants was assayed using cells starved on filters, placed on water pads, and containing different amounts of sorbitol. Development was compared with that of parental Ax2- and STATc- cells (Figure 3). Without stress, there were no major changes in the sizes of the fruiting body in any of the strains. However, in the presence of 100 mM sorbitol—a concentration that hardly affects development of the other two strains—development of the double- strain is almost entirely arrested at an early stage: just a few tiny fruiting bodies are formed. The pattern for the double- strain is similar with 200 mM sorbitol to that at 100 mM, but now STATc- (Thewes et al., 2012) and pyk2− strains form slightly smaller fruiting bodies. These results indicate that Pyk2 and Pyk3 have functions that are additional to the activation of STATc. What might these targets be? There is a major effect of hyperosmotic stress on one specific tyrosine phosphorylation; actin is heavily tyrosine phosphorylated within a few minutes after stress is applied. However, this response is retained in the three mutants (unpublished data).
Affiliation: College of Life Sciences, Welcome Trust Biocentre, University of Dundee, Dundee DD1 5EH, United Kingdom.