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: In marked contrast to other amoebozoans, such as Acanthamoeba (Clarke et al., 2013), Dictyostelium has no orthodox tyrosine kinases, that is, enzymes that contain the diagnostic amino acid sequence tracts that distinguish tyrosine kinases from serine–threonine kinases. However, there are 66 predicted tyrosine kinase–like (TKL) enzymes in the Dictyostelium kinome (Goldberg, Manning, et al., 2006). Five of these, first identified by expressing cDNA libraries in Escherichia coli and immunologically detecting phosphotyrosine in individual bacterial colonies, selectively phosphorylate tyrosine residues (Adler et al., 1996; Nuckolls et al., 1996). Recently we characterized one of them, Pyk2, and showed it to be a direct, constitutive activator of STATc (Araki et al., 2012); in both the presence and the absence of DIF, Pyk2 autophosphorylates on tyrosine residues (Figure 1). Then, via a STATc SH2-domain-Pyk2 phosphotyrosine–mediated interaction, Pyk2 binds to and phosphorylates STATc.
Affiliation: College of Life Sciences, Welcome Trust Biocentre, University of Dundee, Dundee DD1 5EH, United Kingdom.