TABLE 3

List of protein phosphosites in Jurkat cells that are increased by different combinations of PDE inhibitors

Jurkat Cell Data - PGE2 + PDE inhibitorsFold increase over control
GeneDescriptionSite#SequencePGE2 1 nMCIL 5 µMRol 10 µMIC BRL PF8CIL & ROLIBMXPF8 50 µMIBMX PF8 200 µM
RANBP2E3 Sumo-prot lig RanBP21509PRKQSLPA1.71.22.42.24.55.05.2
HIST1H1CHistoneH1.236PRKASGPP1.31.22.41.24.13.23.9
MAGED2Melanoma-assoc antig D2200ARRASRG1.41.21.90.73.81.01.5
SEC22BVesicle-traffic prot SEC22b137RNLGSINT1.31.21.51.43.43.53.5
PWP1Periodic trypt prot 1 homolog485ARNSSISGP1.51.21.81.33.34.43.2
STMN1Stathmin63ERRKSHEA1.21.22.20.43.31.61.9
HIST1H1EHistone H1.437KRKASGP1.61.21.61.93.25.65.4
NUMA1Nucl mitotic apparatus pro11955LRRASMQ1.31.21.41.52.93.63.6
NFRKBNuc factor rel to kappa-B BP310GRKGSLA1.41.21.71.32.92.22.3
CADCAD protein - Dihydroorotase1343GRRLSSFV1.31.21.51.42.95.24.1
MKI6Antigen KI-67538TKRKSLV1.01.01.31.12.53.33.0
DGK2Diacylglycerol kinase zeta163LRRASSHL1.11.61.60.92.61.91.8
  • The fold response of different inhibitors or combinations of inhibitors on the same site in each protein is shown. All but one protein has a good consensus PKA site. Each PDE inhibitor has an isozyme selectivity of at least 30–200-fold if used at appropriate concentrations. From (Beltejar et al., 2017).

  • BRL, BRL50481, a PDE7-selective inhibitor; Cil, cilostamide, a PDE3-selective inhibitor; IBMX, isobutyl-methyl-xanthine, a nonselective inhibitor that targets all PDEs except PDE8; IC, ITI-078, a PDE1-selective inhibitor; PF8, PF-04957325, a selective PDE8 inhibitor; PGE2, prostaglandin E2; Rol, rolipram, a PDE4 selective inhibitor.