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Eukaryotic Cell, February 2007, p. 245-252, Vol. 6, No. 2
1535-9778/07/$08.00+0 doi:10.1128/EC.00204-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.
Adrian Harwood,4
Jeffrey G. Williams,3
Al Ivens,5 and
Catherine Pears1*
Biochemistry Department, Oxford University, South Parks Rd., Oxford OX1 3QU, United Kingdom,1 MRC Laboratory of Molecular Biology, Hills Rd., Cambridge CB2 2QH, United Kingdom,2 School of Life Sciences, Wellcome Trust Biocentre, University of Dundee, Dundee DD1 5EJ, United Kingdom,3 Cardiff School of Biosciences, Cardiff University, Museum Ave., Cardiff CF10 3US, United Kingdom,4 The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, United Kingdom5
Received 28 June 2006/ Accepted 26 October 2006
GskA, the Dictyostelium GSK-3 orthologue, is modified and activated by the dual-specificity tyrosine kinase Zak1, and the two kinases form part of a signaling pathway that responds to extracellular cyclic AMP. We identify potential cellular effectors for the two kinases by analyzing the corresponding null mutants. There are proteins and mRNAs that are altered in abundance in only one or the other of the two mutants, indicating that each kinase has some unique functions. However, proteomic and microarray analyses identified a number of proteins and genes, respectively, that are similarly misregulated in both mutant strains. The positive correlation between the array data and the proteomic data is consistent with the Zak1-GskA signaling pathway's functioning by directly or indirectly regulating gene expression. The discoidin 1 genes are positively regulated by the pathway, while the abundance of the H5 protein is negatively regulated. Two of the targets, H5 and discoidin 1, are well-characterized markers for early development, indicating that the Zak1-GskA pathway plays a role in development earlier than previously observed.
Published ahead of print on 3 November 2006.
Present
address: Universität Konstanz, FB Biologie, Universitätsstrasse 10, 78457 Konstanz, Germany.
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