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Two Dictyostelium tyrosine kinase-like kinases function in parallel, stress-induced STAT activation pathways.

Araki T, Vu LH, Sasaki N, Kawata T, Eichinger L, Williams JG - Mol. Biol. Cell (2014)

Bottom Line: The site(s) that are generated bind the SH2 domain of STATc, and then STATc becomes the target of further kinase action.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.

View Article: PubMed Central - PubMed

Affiliation: College of Life Sciences, Welcome Trust Biocentre, University of Dundee, Dundee DD1 5EH, United Kingdom.

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Scheme for the STATc activation pathways. STATc activation scheme that involves coordinated stress regulation over the phosphatase (PTP3) and the kinase arms (two TKLs; Pyk2 and Pyk3). The calcium/second messenger pathway and the serine/threonine group TKL kinase, Phg2, are involved in PTP3 regulation. The hyperosmotic stress-induced intracellular cGMP increase and the cGMP-binding protein, GbpC, are suggested to affect Pyk2 and Pyk3 activities in the STATc stress response.
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Figure 1: Scheme for the STATc activation pathways. STATc activation scheme that involves coordinated stress regulation over the phosphatase (PTP3) and the kinase arms (two TKLs; Pyk2 and Pyk3). The calcium/second messenger pathway and the serine/threonine group TKL kinase, Phg2, are involved in PTP3 regulation. The hyperosmotic stress-induced intracellular cGMP increase and the cGMP-binding protein, GbpC, are suggested to affect Pyk2 and Pyk3 activities in the STATc stress response.

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.


Two Dictyostelium tyrosine kinase-like kinases function in parallel, stress-induced STAT activation pathways.

Araki T, Vu LH, Sasaki N, Kawata T, Eichinger L, Williams JG - Mol. Biol. Cell (2014)

Scheme for the STATc activation pathways. STATc activation scheme that involves coordinated stress regulation over the phosphatase (PTP3) and the kinase arms (two TKLs; Pyk2 and Pyk3). The calcium/second messenger pathway and the serine/threonine group TKL kinase, Phg2, are involved in PTP3 regulation. The hyperosmotic stress-induced intracellular cGMP increase and the cGMP-binding protein, GbpC, are suggested to affect Pyk2 and Pyk3 activities in the STATc stress response.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4196871&req=5

Figure 1: Scheme for the STATc activation pathways. STATc activation scheme that involves coordinated stress regulation over the phosphatase (PTP3) and the kinase arms (two TKLs; Pyk2 and Pyk3). The calcium/second messenger pathway and the serine/threonine group TKL kinase, Phg2, are involved in PTP3 regulation. The hyperosmotic stress-induced intracellular cGMP increase and the cGMP-binding protein, GbpC, are suggested to affect Pyk2 and Pyk3 activities in the STATc stress response.
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.

Bottom Line: The site(s) that are generated bind the SH2 domain of STATc, and then STATc becomes the target of further kinase action.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.

View Article: PubMed Central - PubMed

Affiliation: College of Life Sciences, Welcome Trust Biocentre, University of Dundee, Dundee DD1 5EH, United Kingdom.

Show MeSH