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Studies of the Fission Yeast Kinome Eukaryotic Cell (in press) Systematic Deletion Analysis of Fission Yeast Protein Kinases. Bimbó A1†, Jia Y2†, Poh SL2,
Murthy Karutiru RK2, den Elzen N3, Peng X2, Zheng L1, O’Connell M3, Liu ET2, Balasubramanian MK1,4*, and Liu J2,5* 1Temasek Life Sciences
Laboratory, 1 Research Link, NUS, Singapore 117604, Singapore; 2Genome
Institute of Singapore, 60 Biopolis Street, Singapore
138672, Singapore; 3Peter MacCallum Cancer Centre, St Andrews Place, Melbourne, Vic
3002, Australia; 4Department
of Biological Sciences, and 5Department of Biochemistry National
University of Singapore, Singapore. Eukaryotic protein kinases are key
molecules mediating signal transduction that play a pivotal role in regulation
of various biological processes including cell cycle progression, cellular
morphogenesis, development, and cellular response to environmental changes. A total of 106 eukaryotic protein kinase
catalytic domain-containing proteins have been found in the entire fission
yeast genome, 44% (or 64%) of which possess orthologues
(or nearest homologues) in humans, based on sequence similarity within
catalytic domains. Systematic deletion
analysis of all putative protein kinase-encoding genes have revealed that 17
out of 106 were essential for viability including three previously
uncharacterized putative protein kinases.
Although the remaining 89 protein kinase mutants were able to form
colonies under optimal growth conditions, 46% of the mutants exhibited
hypersensitivity to at least one of the 17 different stress factors
tested. Phenotypic assessment of these
mutants allowed us to arrange kinases into functional groups. Based on the
results of this assay we propose also the existence of four major signaling
pathways that are involved in response to 17 stresses tested. Microarray analysis demonstrated a
significant correlation between expression signature and growth phenotype of
kinase mutants tested. †Co-first authors; *Corresponding authors
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