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. 2017 Jun 20;114(30):E6240–E6249. doi: 10.1073/pnas.1703939114

Table 1.

Top phosphorylated proteins in response to PDE3 plus PDE4 inhibition in the absence (−) and presence (+) of 1 nM PGE2 compared with changes seen in response to the other PDE inhibitors under the same conditions

Gene Description Position no. Sequence Fold change over control
ITI, BRL, PF8 CIL and ROL IBMX 50 µM IBMX 200 µM
Response to PDE3 and PDE4 inhibitor (−) PGE2
 CAD CAD protein 1,343 GRRLSSFVT 1.10 3.31 2.80 2.86
 RANBP2 E3 SUMO-protein ligase RanBP2 1,509 PRKQSLPAT 1.30 3.17 3.98 4.23
 MAP2K2 Dual specificity mitogen-activated protein kinase kinase 2 394 NQPGTPTRT 0.37 3.01 0.34 0.44
 MAGED2 Melanoma-associated antigen D2 200 ARRASRGPI 0.00 2.92 0.86 1.48
 HIST1H1E Histone H1.4; Histone H1.3 37 KRKASGPPV 1.44 2.82 3.79 4.01
 HIST1H1C Histone H1.2 36 PRKASGPPV 0.89 2.80 2.37 2.61
 UBE2O E2/E3 hybrid ubiquitin-protein ligase UBE2O 515 SRKKSIPLS 0.66 2.52 1.93 0.95
 RCSD1 CapZ-interacting protein 108 ASPKSPGLK 1.54 2.27 0.69 1.05
 ATAD2 ATPase family AAA domain-containing protein 2 1,302 RARRSQVEQ 1.24 2.23 3.53 3.92
 SEC22B Vesicle-trafficking protein SEC22b 137 RNLGSINTE 1.21 2.16 2.68 2.89
 GAS2L1 GAS2-like protein 1 316 ERRGSRPEM 1.25 2.15 2.32 1.67
 SSH2 Protein phosphatase Slingshot homolog 2 811 PKKNSIHEL 1.41 2.13 1.87 2.19
Response to PDE3 and PDE4 inhibitor (+) PGE2
 RANBP2 E3 SUMO-protein ligase RanBP2 1,509 PRKQSLPAT 2.20 4.51 5.01 5.21
 HIST1H1C Histone H1.2 36 PRKASGPPV 1.23 4.05 3.23 3.88
 MAGED2 Melanoma-associated antigen D2 200 ARRASRGPI 0.68 3.84 1.02 1.53
 SEC22B Vesicle-trafficking protein SEC22b 137 RNLGSINTE 1.44 3.36 3.45 3.50
 PWP1 Periodic tryptophan protein 1 homolog 485 ARNSSISGP 1.27 3.29 4.42 3.20
 STMN1 Stathmin 63 ERRKSHEAE 0.42 3.25 1.57 1.59
 HIST1H1E Histone H1.4 37 KRKASGPPV 1.94 3.17 5.58 5.42
 NUMA1 Nuclear mitotic apparatus protein 1 1,955 LRRASMQPI 1.49 2.91 3.59 3.59
 NFRKB Nuclear factor related to kappa-B-BP 310 GRKGSLAAL 1.28 2.88 2.17 2.33
 CAD CAD protein 1,343 GRRLSSFVT 1.41 2.87 5.24 4.13
 MKI67 Antigen KI-67 538 TKRKSLVMH 1.14 2.53 3.25 3.02

Consensus PKA primary amino acid phosphorylation sequences are shown in bold, underlined, italicized text. Statistically significantly regulated changes in phosphorylation in the other PDE inhibitor conditions (P < 0.05) are shown in bold. BRL, BRL50481; CIL, cilostamide; ITI, ITI-078; PF8, PF-04957325; ROL, rolipram.

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