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
Mentions: To determine the effects of the various mutations on specific gene expression, we analyzed, by quantitative real-time PCR (qPCR), the sorbitol induction of three genes known to require STATc for their optimal inducibility: rtoA, sigG, and an uncharacterized gene (Dictybase ID DDB_G0277667). The three genes are maximally induced in the parental (Ax2) strain and somewhat less well induced in the pyk2− or pyk3− strain (Figure 4A). In the double- strain, and as expected in the STATc- strain, sorbitol inducibility is abolished and there is even, perhaps, slight repression of gene expression by sorbitol.
Affiliation: College of Life Sciences, Welcome Trust Biocentre, University of Dundee, Dundee DD1 5EH, United Kingdom.