Research Article

Identifying Functional Mechanisms of Gene and Protein Regulatory Networks in Response to a Broader Range of Environmental Stresses

Table 1

Under hypo-osmotic stress (a), sorbitol osmotic stress (b), and pheromone stress (c), the listed target proteins are interacted by at least five preselected proteins. According to the literature evidence, target proteins can be grouped, respectively, into the functional pathways denoted by P (pheromone response pathway), O (SHO1 branch of the HOG pathway), N (SLN1 branch of the HOG pathway) and I (cell-wall integrity pathway). The RV of each PPI is also given inside the brackets. A protein interaction with smaller RV implies a more significant protein interaction. New found target proteins are highlighted with the color gray.
(a) Hypo-osmotic stress

Target proteinLiterature evidenceUpstream proteins within 40 preselected proteins

 [58]SLN1 (0.050)HOG1 (0.054)STE50 (0.091)CDC42 (0.095)SSK2 (0.122)STE20 (0.163)OPY2 (0.181)STE11 (0.272)SHO1 (0.299)PTP2 (0.560)YPD1 (0.578)SSK22 (0.905)
 [48, 23]STE11 (0.016)SSK2 (0.018)GPD1 (0.025)PTP2 (0.041)PTC1 (0.222)YPD1 (0.249)SSK1 (0.295)FPS1 (0.531)HOG1 (0.578)SHO1 (0.819)
 [4, 5, 7, 8]YPD1 (0.100)SSK1 (0.140)SSK2 (0.143)SLN1 (0.160)PTC1 (0.320)STE20 (0.325)HOG1 (0.330)BCK1 (0.338)PBS2 (0.500)
 [68]STE5 (0.047)STE4 (0.208)SSK1 (0.271)SSK22 (0.286)STE50 (0.306)SSK2 (0.443)SHO1 (0.479)STE11 (0.627)
 [6]CDC24 (0.015)STE20 (0.028)CLA4 (0.049)CDC42 (0.056)HOG1 (0.185)SHO1 (0.432)KSS1 (0.441)STE12 (0.667)
 [7]CDC24 (0.045)KSS1 (0.079)STE7 (0.095)STE50 (0.431)STE20 (0.556)STE12 (0.739)STE2 (0.958)
 [68]STE11 (0.035)KSS1 (0.125)STE5 (0.180)STE7 (0.187)STE4 (0.412)STE12 (0.630)
 [68]HOG1 (0.030)SLN1 (0.060)PTP2 (0.200)PBS2 (0.200)SSK2 (0.280)SSK1 (0.640)
 [24]KSS1 (0.014)STE3 (0.236)STE5 (0.267)STE20 (0.365)STE12 (0.391)CLA4 (0.396)
 [58]HOG1 (0.024)PTC1 (0.111)SSK1 (0.166)PTP2 (0.291)SHO1 (0.457)YPD1 (0.571)
 [48, 23]PKC1 (0.009)RAS2 (0.067)SSK22 (0.104)HOG1 (0.124)SHO1 (0.148)PTP2 (0.260)
 [7, 8]SLT2 (0.080)MID2 (0.125)FPS1 (0.130)PKC1 (0.158)MKK1 (0.316)BCK1 (0.656)
 [4, 7, 8]PKC1 (0.004)MID2 (0.045)PTP2 (0.221)RHO1 (0.238)SLT2 (0.416)BCK1 (0.544)

(b) Sorbitol osmotic stress

Target proteinLiterature evidenceUpstream proteins within 40 preselected proteins

 [7]STE12 (0.001)TEC1 (0.005)PKC1 (0.006)HOG1 (0.014)STE50 (0.015)RHO1 (0.017)STE11 (0.020)STE7 (0.021)STE20 (0.023)CDC24 (0.024)STE2 (0.037)STE5 (0.209)STE3 (0.236)
 [48, 23]SHO1 (0.001)SSK1 (0.002)MSB2 (0.003)HOG1 (0.004)SSK2 (0.006)STE11 (0.007)PKC1 (0.008)STE50 (0.013)STE20 (0.014)PBS2 (0.017)SLN1 (0.024)
 [48, 23]TEC1 (0.003)STE20 (0.004)KSS1 (0.007)SSK1 (0.010)STE7 (0.011)STE11 (0.014)CLA4 (0.014)SHO1 (0.016)GPD1 (0.017)STE4 (0.025)STE5 (0.516)
 [4, 5, 7, 8]SSK2 (0.020)PTC1 (0.045)HOG1 (0.180)PTP3 (0.195)BCK1 (0.200)SSK1 (0.213)SLT2 (0.360)STE20 (0.405)PBS2 (0.413)SLN1 (0.500)YPD1 (0.525)
 [68, 23]STE50 (0.022)SSK1 (0.074)CDC42 (0.095)SSK2 (0.111)STE4 (0.118)STE5 (0.231)SSK22 (0.249)STE11 (0.281)SHO1 (0.391)OPY2 (0.408)
 [7]KSS1 (0.003)CDC24 (0.011)STE11 (0.013)HOG1 (0.024)STE7 (0.026)STE12 (0.030)STE50 (0.031)STE5 (0.073)STE4 (0.333)STE2 (0.809)
 [48, 23]KSS1 (0.002)RAS2 (0.004)STE11 (0.009)PKC1 (0.010)PTP2 (0.011)YPD1 (0.012)SSK22 (0.017)HOG1 (0.019)PTC1 (0.023)SHO1 (0.026)
 [48, 23]SSK2 (0.014)STE50 (0.058)GPD1 (0.080)FPS1 (0.086)HOG1 (0.144)PTC1 (0.154)PTP2 (0.168)YPD1 (0.229)SSK1 (0.288)STE11 (0.736)
 [48, 23]HOG1 (0.061)PTP2 (0.092)STE50 (0.092)YPD1 (0.112)SSK22 (0.163)SSK2 (0.255)STE11 (0.357)SHO1 (0.643)STE20 (0.796)
 [7, 8]STE7 (0.002)STE11 (0.004)STE20 (0.006)MSB2 (0.012)RAS2 (0.014)STE5 (0.289)STE4 (0.351)STE2 (0.907)
 [5]STE11 (0.001)GPD1 (0.003)HOG1 (0.007)MID2 (0.009)SSK22 (0.011)FPS1 (0.014)SSK2 (0.016)SLT2 (0.017)
 [6]HOG1 (0.048)CDC42 (0.097)STE12 (0.104)CDC24 (0.135)CLA4 (0.228)KSS1 (0.249)STE20 (0.824)
 [25]STE11 (0.007)STE12 (0.011)CDC42 (0.021)CDC24 (0.022)SSK2 (0.023)STE5 (0.086)STE4 (0.296)
 [7]SLT2 (0.001)SSK2 (0.005)STE7 (0.010)CLA4 (0.012)STE11 (0.015)RAS2 (0.016)STE12 (0.022)
 [4, 5, 7, 23]CLA4 (0.001)SSK2 (0.002)PBS2 (0.004)PKC1 (0.007)PTP2 (0.010)SLN1 (0.015)
 [23]SSK2 (0.025)PTC1 (0.044)BCK1 (0.127)PTP2 (0.222)STE20 (0.452)SLT2 (0.645)
 [26]MSB2 (0.180)STE50 (0.413)STE20 (0.471)CDC24 (0.645)CLA4 (0.676)CDC42 (0.712)
 [7]KSS1 (0.050)CLA4 (0.223)STE20 (0.331)STE7 (0.331)STE12 (0.347)STE11 (0.744)
[7, 27]STE7 (0.051)STE5 (0.112)STE2 (0.147)STE4 (0.357)STE12 (0.388)STE11 (0.520)
 [4, 7]PKC1 (0.005)YPD1 (0.009)CDC42 (0.009)SLN1 (0.011)PTC1 (0.014)RHO1 (0.016)
 [28]STE50 (0.001)KSS1 (0.015)SHO1 (0.016)STE4 (0.175)STE5 (0.242)STE2 (0.623)
 [29]RHO1 (0.032)SSK22 (0.036)STE11 (0.041)PKC1 (0.100)SSK2 (0.215)MID2 (0.299)
 [4]CLA4 (0.001)SWI6 (0.010)STE20 (0.015)CDC42 (0.020)PTC1 (0.026)STE3 (0.051)
 [30]CLA4 (0.001)RHO1 (0.006)CDC42 (0.007)STE20 (0.019)PBS2 (0.032)STE4 (0.442)
 [4, 7, 8]PKC1 (0.028)RHO1 (0.038)BCK1 (0.061)SLT2 (0.153)MID2 (0.436)PTP2 (0.670)
 [31]CLA4 (0.006)HKR1 (0.011)CDC24 (0.016)CDC42 (0.019)STE20 (0.021)RHO1 (0.025)

(c) Pheromone stress

Target ProteinLiterature evidenceUpstream proteins within 40 preselected proteins

[68, 23]STE4 (0.001)STE3 (0.002)STE5 (0.008)CLA4 (0.010)MSB2 (0.016)SSK1 (0.016)STE12 (0.069)RAS2 (0.080)CDC24 (0.175)PTP2 (0.342)SLT2 (0.471)CDC42 (0.535)SHO1 (0.634)
[48, 23]STE5 (0.001)STE4 (0.002)SSK2 (0.035)YPD1 (0.099)MSB2 (0.109)PTP2 (0.202)SSK1 (0.235)FPS1 (0.265)SHO1 (0.385)PTC1 (0.393)SLN1 (0.417)PTP3 (0.420)STE11 (0.718)
[7]STE5 (0.012)STE3 (0.019)STE2 (0.022)RHO1 (0.036)STE50 (0.126)PKC1 (0.128)STE7 (0.201)KSS1 (0.231)STE20 (0.261)HOG1 (0.365)STE12 (0.370)STE11 (0.373)CDC24 (0.544)
[68, 23]SSK1 (0.011)STE50 (0.023)STE5 (0.106)OPY2 (0.251)SSK22 (0.318)SHO1 (0.321)SSK2 (0.416)CDC42 (0.539)STE4 (0.739)STE11 (0.749)
[48, 23]PBS2 (0.029)SSK1 (0.102)STE11 (0.132)MSB2 (0.165)STE50 (0.217)HKR1 (0.260)SSK2 (0.263)HOG1 (0.607)SHO1 (0.640)STE20 (0.725)
[7]MKK1 (0.070)STE7 (0.085)PKC1 (0.162)CLA4 (0.188)RAS2 (0.234)STE11 (0.304)SSK2 (0.444)RHO1 (0.609)SLT2 (0.641)STE12 (0.672)
[4, 7, 8]STE4 (0.010)PBS2 (0.063)SLT2 (0.080)SHO1 (0.187)BCK1 (0.313)RHO1 (0.340)MKK1 (0.365)PTC1 (0.644)MID2 (0.819)
[4, 24, 32]STE4 (0.004)RHO1 (0.009)STE5 (0.009)CDC42 (0.033)CDC24 (0.037)STE7 (0.045)CLA4 (0.065)STE20 (0.245)STE11 (0.411)
[7]STE5 (0.012)STE4 (0.060)STE12 (0.151)HOG1 (0.173)STE11 (0.230)CDC24 (0.235)STE2 (0.303)STE50 (0.346)KSS1 (0.560)
[7, 8]STE4 (0.012)STE5 (0.016)STE7 (0.076)STE12 (0.078)RAS2 (0.109)TEC1 (0.180)STE20 (0.217)MSB2 (0.431)STE11 (0.657)
[48, 23]SHO1 (0.003)YPD1 (0.005)RAS2 (0.010)PTC1 (0.011)PKC1 (0.021)KSS1 (0.022)SSK2 (0.025)HOG1 (0.026)SSK22 (0.029)
[48, 23]SSK2 (0.009)SSK1 (0.034)PBS2 (0.106)HOG1 (0.106)STE50 (0.227)SHO1 (0.386)YPD1 (0.431)FPS1 (0.484)PTC1 (0.567)
[4, 5, 7, 8]PBS2 (0.039)MKK1 (0.039)HOG1 (0.047)BCK1 (0.150)PTP3 (0.249)SSK2 (0.266)PTC1 (0.288)SSK1 (0.305)SLT2 (0.798)
[4, 7, 33, 34]SWI6 (0.001)STE4 (0.001)STE11 (0.003)CLA4 (0.007)SLT2 (0.009)CDC42 (0.074)STE20 (0.096)RAS2 (0.525)PKC1 (0.552)
[23]PTP2 (0.021)STE20 (0.065)PBS2 (0.120)HOG1 (0.477)SSK2 (0.529)SLT2 (0.567)BCK1 (0.645)PTC1 (0.696)
[4, 7, 8]HKR1 (0.003)MKK1 (0.065)PTP2 (0.139)BCK1 (0.164)SLT2 (0.166)PKC1 (0.250)CLA4 (0.267)MID2 (0.911)
[68]STE4 (0.022)STE12 (0.031)HOG1 (0.179)STE7 (0.190)PBS2 (0.237)TEC1 (0.305)MSB2 (0.692)
[35, 36]SLT2 (0.029)PKC1 (0.236)CLA4 (0.251)FPS1 (0.340)BCK1 (0.380)PTC1 (0.650)MID2 (0.790)
[5]MID2 (0.028)STE11 (0.047)SSK22 (0.053)SSK2 (0.063)GPD1 (0.202)SLT2 (0.260)HOG1 (0.709)
[7, 37, 38]RHO1 (0.000)CDC42 (0.000)STE11 (0.004)CLA4 (0.005)STE12 (0.006)PKC1 (0.009)BCK1 (0.011)
[5, 6]MSB2 (0.001)CDC24 (0.002)SLT2 (0.003)BCK1 (0.003)STE20 (0.006)STE11 (0.006)CDC42 (0.007)
[4, 5, 7, 23]SSK2 (0.070)PKC1 (0.107)PTP2 (0.172)PBS2 (0.342)HOG1 (0.680)SLT2 (0.736)
[68]STE5 (0.012)STE4 (0.089)STE12 (0.130)STE7 (0.331)STE11 (0.385)KSS1 (0.568)
[4, 7, 8]BCK1 (0.001)PKC1 (0.001)MID2 (0.003)FPS1 (0.003)PTC1 (0.006)CLA4 (0.007)
[25]SSK2 (0.008)STE12 (0.010)STE5 (0.011)CDC42 (0.021)CDC24 (0.029)STE4 (0.035)
[7, 8]SLT2 (0.019)MID2 (0.019)FPS1 (0.065)MKK1 (0.083)PKC1 (0.150)RHO1 (0.166)
[4, 7]MKK1 (0.009)SLT2 (0.030)MID2 (0.050)RHO1 (0.191)PKC1 (0.332)PTC1 (0.414)
[4]STE3 (0.027)PTC1 (0.125)CLA4 (0.131)SWI6 (0.150)STE20 (0.197)CDC42 (0.312)
[4, 7, 8]BCK1 (0.022)PTP2 (0.104)SLT2 (0.196)PKC1 (0.329)RHO1 (0.678)MID2 (0.726)
[31]PKC1 (0.009)RHO1 (0.015)CDC24 (0.018)CDC42 (0.020)CLA4 (0.024)HKR1 (0.027)