TABLE 3.

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

Jurkat Cell Data - PGE2 + PDE inhibitors				Fold increase over control
Gene	Description	Site#	Sequence	PGE2 1 nM	CIL 5 µM	Rol 10 µM	IC BRL PF8	CIL & ROL	IBMXPF8 50 µM	IBMX PF8 200 µM
RANBP2	E3 Sumo-prot lig RanBP2	1509	PRKQSLPA	1.7	1.2	2.4	2.2	4.5	5.0	5.2
HIST1H1C	HistoneH1.2	36	PRKASGPP	1.3	1.2	2.4	1.2	4.1	3.2	3.9
MAGED2	Melanoma-assoc antig D2	200	ARRASRG	1.4	1.2	1.9	0.7	3.8	1.0	1.5
SEC22B	Vesicle-traffic prot SEC22b	137	RNLGSINT	1.3	1.2	1.5	1.4	3.4	3.5	3.5
PWP1	Periodic trypt prot 1 homolog	485	ARNSSISGP	1.5	1.2	1.8	1.3	3.3	4.4	3.2
STMN1	Stathmin	63	ERRKSHEA	1.2	1.2	2.2	0.4	3.3	1.6	1.9
HIST1H1E	Histone H1.4	37	KRKASGP	1.6	1.2	1.6	1.9	3.2	5.6	5.4
NUMA1	Nucl mitotic apparatus pro1	1955	LRRASMQ	1.3	1.2	1.4	1.5	2.9	3.6	3.6
NFRKB	Nuc factor rel to kappa-B BP	310	GRKGSLA	1.4	1.2	1.7	1.3	2.9	2.2	2.3
CAD	CAD protein - Dihydroorotase	1343	GRRLSSFV	1.3	1.2	1.5	1.4	2.9	5.2	4.1
MKI6	Antigen KI-67	538	TKRKSLV	1.0	1.0	1.3	1.1	2.5	3.3	3.0
DGK2	Diacylglycerol kinase zeta	163	LRRASSHL	1.1	1.6	1.6	0.9	2.6	1.9	1.8

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.