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.