In Saccharomyces cerevisiae, disruption of both protein phosphatase genes, PTP2 and MSG5, causes calcium sensitivity while additional disruption of protein Idnase genes BCK1, MKK1, SLT2, MCK1 YAK1 and SSK2 confers calcium tolerance. Although the roles of BCKI, MICK1 and SLT2 have been characterized recently, the mechanism of suppression of the calcium sensitivity by SSK2 disruption is poorly understood. In this study, genetic analysis revealed a novel, high osmolarity glycerol (HOG)-independent suppressor function of Ssk2 in relation to the Ptp2 and Msg5-mediated calcium signaling. Through microarray analysis, we identified 19 genes with distinct pattern of expression that is likely involved in the calcium sensitive phenotype of the ptp2 Delta msg5 Delta double disruptant. Furthermore, we found msn2 Delta and bcy1 Delta as suppressors of the calcium sensitive phenotype. Our results suggest the interrelationship of a HOG-independent function of Ssk2, transcription factor Msn2, protein kinase A-related protein Bcyl and 19 rise and fall genes as responsible for the suppression mechanism of the ptp2 Delta msg5 Delta double disruptant by ssk2 Delta disruption. (C) 2013, The Society for Biotechnology, Japan. All rights reserved.