pde2a  (Santa Cruz Biotechnology)

Journal: Frontiers in Pharmacology

Article Title: Metabolic profiling of the TME uncovers the contrasting impacts of CKMT2 and PDE2A in CRC progression and therapeutic response

doi: 10.3389/fphar.2026.1732137

Figure Lengend Snippet: Prognostic TMET genes defining TMET subtype phenotypes. (A) Univariate Cox regression analysis of TMET crosstalk genes in CRC. (B) Heatmap of the top 28 prognostically relevant TMET genes with significant differential expression (|logFC| > 0.15). (C,D) KEGG pathway enrichment of C1- and C2-upregulated TMET genes. (E,F) Kaplan–Meier survival curves stratified by CKMT2 and PDE2A expression. (G) PCA plot showing subtype separation driven by CKMT2 and PDE2A expression. (H) ROC curves evaluating the discriminatory performance of CKMT2 and PDE2A.

Article Snippet: Membranes were blocked with 5% bovine serum albumin (BSA) in TBST buffer and incubated overnight at 4 °C with a primary antibody against CKMT2 (Proteintech, #23995-1-AP, Rabbit, 1:1,000) and PDE2A (Proteintech, #55306-1-AP,Rabbit, 1:1,000).

Techniques: Quantitative Proteomics, Expressing

Journal: Frontiers in Pharmacology

Article Title: Metabolic profiling of the TME uncovers the contrasting impacts of CKMT2 and PDE2A in CRC progression and therapeutic response

doi: 10.3389/fphar.2026.1732137

Figure Lengend Snippet: Single-cell resolution of TMET gene expression. (A,B) t-SNE plots showing major cell populations in CRC single-cell datasets EMTAB8107 and GSE166555 . (C,D) Distribution of malignant, immune, and stromal lineages across datasets. (E–H) Expression patterns of C1- and C2-associated TMET genes in EMTAB8107. (I–L) Corresponding expression patterns in GSE166555 . (M–P) Dot plots showing TMET gene expression across cell types. (Q–T) t-SNE plots illustrating PDE2A and CKMT2 expression in both datasets. C1: high-risk; C2: low-risk.

Article Snippet: Membranes were blocked with 5% bovine serum albumin (BSA) in TBST buffer and incubated overnight at 4 °C with a primary antibody against CKMT2 (Proteintech, #23995-1-AP, Rabbit, 1:1,000) and PDE2A (Proteintech, #55306-1-AP,Rabbit, 1:1,000).

Techniques: Single Cell, Gene Expression, Expressing

Journal: Frontiers in Pharmacology

Article Title: Metabolic profiling of the TME uncovers the contrasting impacts of CKMT2 and PDE2A in CRC progression and therapeutic response

doi: 10.3389/fphar.2026.1732137

Figure Lengend Snippet: Risk stratification based on PDE2A and CKMT2. (A,B) Risk stratification of CRC patients using LASSO regression based on PDE2A and CKMT2 expression. (C) Bar plot illustrating the distribution of CRC patients according to risk scores derived from PDE2A and CKMT2. (D) Kaplan-Meier survival curve comparing overall survival (OS) between risk subgroups. (E) Sankey diagram mapping the distribution of CRC patients across molecular clusters, risk subgroups, PDE2A and CKMT2 expression levels, and vital status. (F) PCA plot visualizing the dimensional separation of risk subgroups. (G) PCA plot depicting the segregation of gene-based subgroups. (H) Heatmap displaying PDE2A and CKMT2 expression across risk subgroups and their associations with clinical and molecular features. (I–L) Bar plots showing the distribution of gene-based subtypes across cancer stages and molecular classifications, including MSI, CMS, and CIMP status.

Article Snippet: Membranes were blocked with 5% bovine serum albumin (BSA) in TBST buffer and incubated overnight at 4 °C with a primary antibody against CKMT2 (Proteintech, #23995-1-AP, Rabbit, 1:1,000) and PDE2A (Proteintech, #55306-1-AP,Rabbit, 1:1,000).

Techniques: Expressing, Derivative Assay

Journal: Frontiers in Pharmacology

Article Title: Metabolic profiling of the TME uncovers the contrasting impacts of CKMT2 and PDE2A in CRC progression and therapeutic response

doi: 10.3389/fphar.2026.1732137

Figure Lengend Snippet: Validation of PDE2A and CKMT2 in colorectal cancer. (A,C) GEPIA-based comparison of CKMT2 and PDE2A mRNA expression in normal and CRC tissues. (B,D) qPCR validation in FHC, SW480, and HCT116 cell lines. (E–H) Western blot analysis and quantification of CKMT2 and PDE2A protein expression. (I,J) Representative IHC images and quantitative comparison in CRC and adjacent normal tissues (n = 63). (K) Heatmap of protein expression in relation to clinicopathological features. (L,M) Representative IHC images and Pearson correlation analysis showing inverse expression of CKMT2 and PDE2A.

Article Snippet: Membranes were blocked with 5% bovine serum albumin (BSA) in TBST buffer and incubated overnight at 4 °C with a primary antibody against CKMT2 (Proteintech, #23995-1-AP, Rabbit, 1:1,000) and PDE2A (Proteintech, #55306-1-AP,Rabbit, 1:1,000).

Techniques: Biomarker Discovery, Comparison, Expressing, Western Blot

Journal: Frontiers in Pharmacology

Article Title: Metabolic profiling of the TME uncovers the contrasting impacts of CKMT2 and PDE2A in CRC progression and therapeutic response

doi: 10.3389/fphar.2026.1732137

Figure Lengend Snippet: External validation of the prognostic impact of PDE2A and CKMT2. (A,B) Kaplan-Meier survival curves illustrating differences in recurrence-free survival (RFS, n = 1,336) and overall survival (OS, n = 1,061) between CRC patients with high and low PDE2A expression. (C,D) Kaplan-Meier survival curves depicting differences in recurrence-free survival (RFS, n = 1,336) and overall survival (OS, n = 1,061) between CRC patients with high and low CKMT2 expression.

Article Snippet: Membranes were blocked with 5% bovine serum albumin (BSA) in TBST buffer and incubated overnight at 4 °C with a primary antibody against CKMT2 (Proteintech, #23995-1-AP, Rabbit, 1:1,000) and PDE2A (Proteintech, #55306-1-AP,Rabbit, 1:1,000).

Techniques: Biomarker Discovery, Expressing

Journal: Frontiers in Pharmacology

Article Title: Metabolic profiling of the TME uncovers the contrasting impacts of CKMT2 and PDE2A in CRC progression and therapeutic response

doi: 10.3389/fphar.2026.1732137

Figure Lengend Snippet: Impact of PDE2A and CKMT2 on immunotherapy response. (A,B) Kaplan-Meier survival curves showing overall survival (OS, n = 1,061) differences between patients with high and low PDE2A and CKMT2 expression. (C,D) Box plot and ROC curves comparing PDE2A expression between immunotherapy responders (n = 355) and non-responders (n = 570). (E,F) Box plot and ROC curves comparing CKMT2 expression between immunotherapy responders (n = 355) and non-responders (n = 570).

Article Snippet: Membranes were blocked with 5% bovine serum albumin (BSA) in TBST buffer and incubated overnight at 4 °C with a primary antibody against CKMT2 (Proteintech, #23995-1-AP, Rabbit, 1:1,000) and PDE2A (Proteintech, #55306-1-AP,Rabbit, 1:1,000).

Techniques: Expressing

Journal: Journal of the American Heart Association

Article Title: Cardiac Gene Therapy With Phosphodiesterase 2A Limits Remodeling and Arrhythmias in Mouse Models of Heart Failure

doi: 10.1161/jaha.124.037343

Figure Lengend Snippet: Figure 2. Gene therapy with PDE2A prevents cardiac remodeling and dysfunction induced by chronic isoproterenol infusion. A, Schematic representation of the experimental protocol. Mice were injected in the tail vein with 1012 viral particles of a serotype 9 adeno-associated viruses encoding for luciferase or phosphodiesterase 2A3. Fourteen days later, mice injected with AAV9-LUC were implanted subcutaneously with osmotic pumps diffusing either NaCl (NaCl-LUC) or isoproterenol at 60 mg/kg per day (isoproterenol- LUC) and animals injected with AAV9-PDE2A were implanted with pumps delivering isoproterenol at 60 mg/kg per day (isoproterenol- PDE2A). Treatment duration was 14 days (hatched bars). Minipumps were then removed and mice were kept for 2 additional weeks before euthanasia. Cardiac function was evaluated by serial echocardiography before injection of the virus as well as at 14, 28, 35, and 42 days. B, Left panel shows representative blots of PDE2A and vinculin. PDE2A protein expression in heart tissues extracts measured by Western blot and the bar graph represents the ratios of PDE2A over vinculin quantified expressed as mean±SEM in NaCl-LUC, isoproterenol-LUC and isoproterenol-PDE2A groups. C, Heart weight and lung weight over tibia length ratio expressed as mean±SEM. D, Time course of the normalized ratio of calculated left ventricular weight over body weight and normalized ejection fraction in NaCl-LUC, isoproterenol-LUC and isoproterenol-PDE2A mice. Number of mice is indicated in the brackets. E, Panel on the left, representative images of Masson’s trichrome staining (scale bar 100 μm), bar graph on the left represents quantifications of interstitial fibrosis as mean±SEM in NaCl-LUC (n=9), isoproterenol-LUC (n=9), and isoproterenol+PDE2A (n=9) groups. Statistical significance is indicated by the P value (* vs NaCl-LUC and † vs isoproterenol-LUC) determined using Welch’s t test (B), Kruskal– Wallis followed by a Dunn’s test (C panel bottom and E), 2-way ANOVA followed by a Tukey’s test (D), 1-way ANOVA followed by a Tukey’s test (C panel top). AAV9 indicates serotype 9 adeno-associated viruses; BW, body weight; HW, heart weight; Iso-LUC, isoproterenol-luciferase; Iso-PDE2A, isoproterenol-phosphodiesterase 2A; LUC, luciferase; LVW, left ventricular weight; LW, lung weight; PDE2A, phosphodiesterase 2A; and TL, tibia length.

Article Snippet: The primary antibodies used were as follows: (1) Figure 1: rabbit anti- PDE2A, Fabgennix; PDE2A- 101AP diluted at 1/1000; rabbit anti- GAPDH, Cell Signaling, 2118 diluted at 1/1000; (2) Figure 2: goat antiPDE2A, Santa Cruz, SC- 17228 diluted at 1/1000; mouse anti- vinculin, V9131 Sigma- Aldrich diluted at 1/1000; (3) Figure 3: rabbit anti- PDE2A, Fabgennix, PDE2A- 101AP diluted at 1/1000; rabbit anti- GAPDH, Cell Signaling, 2118 diluted at 1/1000; (4) Figure S1: rabbit anti- flag L5, Novus Biologicals, NBP1- 06712 diluted at 1/500; rabbit anti- GAPDH, Cell Signaling, 2118 diluted at 1/1000; rabbit anti- PDE2A, Proteintech, 55 306- 1- AP diluted at 1/1000; rabbit anti- flag L5, Novus Biologicals, NBP1- 06712 diluted at 1/500; rabbit anti- GAPDH, Cell Signaling, 2118 diluted at 1/1000; (5) Figure S2B: rabbit anti- PDE2A, Proteintech, 55 306- 1- AP diluted at 1/1000; (6) Figure S3: rabbit antiPDE2A, Proteintech, 55 306- 1- AP diluted at 1/1000; and (7) Figure S4: rabbit anti- PDE4A AC55 (gift from Dr. Marco Conti, University of California San Francisco, San Francisco, CA) diluted at 1/1000; rabbit anti- PDE4B (gift from Dr. Marco Conti) diluted at 1/10000; mouse antiPDE4D (gift from Dr Marco Conti) diluted at 1/1000 and rabbit anti- PDE3A (gift from Dr Chen Yan, University of Rochester, Rochester, NY) diluted at 1/10000.

Techniques: Injection, Luciferase, Virus, Expressing, Western Blot, Staining

Journal: Journal of the American Heart Association

Article Title: Cardiac Gene Therapy With Phosphodiesterase 2A Limits Remodeling and Arrhythmias in Mouse Models of Heart Failure

doi: 10.1161/jaha.124.037343

Figure Lengend Snippet: Figure 3. PDE2A overexpression limits maladaptive remodeling and cardiac dysfunction induced by chronic isoproterenol and phenylephrine infusion. A, Schematic representation of the experimental protocol. Mice were injected with 1012 viral particles of serotype 9 adeno-associated viruses encoding for Luciferase or phosphodiesterase 2A3. Fourteen days later, mice were implanted with osmotic minipumps diffusing either NaCl (NaCl-LUC) or isoproterenol+phenylephrine at 30 mg/kg per day each (isoproterenol+phenylephrine-LUC and isoproterenol + phenylephrine-PDE2A). Minipumps were removed 2 weeks later and mice were euthanized. Cardiac function was assessed throughout the protocol using echocardiography before the injection of the virus and at 2, 3, 4, and 6 weeks. B, Representative blots of PDE2A and GAPDH on the left panel are shown and the bar graph represents ratios of PDE2A over GAPDH quantifications expressed as mean±SEM in a subset of the animals treated with NaCl-LUC, isoproterenol+phenylephrine-LUC, and isoproterenol+phenylephrine-PDE2A. C, Heart weight and lung weight over tibia length ratios expressed as mean±SEM. D, Time course of the normalized ratios of calculated left ventricular weight (over body weight and normalized ejection fraction in NaCl-LUC, isoproterenol+phenylephrine-LUC, and isoproterenol+phenylephrine-PDE2A mice). Number of mice is indicated in the brackets. E, Top panel shows representative images of Masson’s trichrome staining (scale bar 200 μm), the middle panel depicts representative images of terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay (scale bar 100 μm) detecting apoptotic nuclei in green costained with the glycocalix marker wheat germ agglutinin in red and nuclei in blue colored with Hoechst. Bar graphs representing mean±SEM quantifications of interstitial fibrosis and apoptotic nuclei in NaCl-LUC (10), isoproterenol+phenylephrine- LUC (9) and isoproterenol+phenylephrine-PDE2A (9) mice are depicted. Statistical significance indicated by the P value (* vs NaCl- LUC and † vs isoproterenol+phenylephrine-LUC) was determined using Welch’s t test (B), Kruskal–Wallis followed by a Dunn’s test (C), 2-way ANOVA followed by a Tukey’s test (D), Welch’s 1-way ANOVA followed by a Dunnett’s test (E). AAV9 indicates serotype 9 adeno-associated viruses; BW, body weight; HW, heart weight; Iso-Phe-LUC, isoproterenol-phenylephrine-luciferase; Iso-Phe- PDE2A, isoproterenol-phenylephrine-phosphodiesterase 2A; LUC, luciferase; LVW, left ventricular weight; LW, lung weight; ns, not significant; PDE2A, phosphodiesterase 2A; and TL, tibia length.

Article Snippet: The primary antibodies used were as follows: (1) Figure 1: rabbit anti- PDE2A, Fabgennix; PDE2A- 101AP diluted at 1/1000; rabbit anti- GAPDH, Cell Signaling, 2118 diluted at 1/1000; (2) Figure 2: goat antiPDE2A, Santa Cruz, SC- 17228 diluted at 1/1000; mouse anti- vinculin, V9131 Sigma- Aldrich diluted at 1/1000; (3) Figure 3: rabbit anti- PDE2A, Fabgennix, PDE2A- 101AP diluted at 1/1000; rabbit anti- GAPDH, Cell Signaling, 2118 diluted at 1/1000; (4) Figure S1: rabbit anti- flag L5, Novus Biologicals, NBP1- 06712 diluted at 1/500; rabbit anti- GAPDH, Cell Signaling, 2118 diluted at 1/1000; rabbit anti- PDE2A, Proteintech, 55 306- 1- AP diluted at 1/1000; rabbit anti- flag L5, Novus Biologicals, NBP1- 06712 diluted at 1/500; rabbit anti- GAPDH, Cell Signaling, 2118 diluted at 1/1000; (5) Figure S2B: rabbit anti- PDE2A, Proteintech, 55 306- 1- AP diluted at 1/1000; (6) Figure S3: rabbit antiPDE2A, Proteintech, 55 306- 1- AP diluted at 1/1000; and (7) Figure S4: rabbit anti- PDE4A AC55 (gift from Dr. Marco Conti, University of California San Francisco, San Francisco, CA) diluted at 1/1000; rabbit anti- PDE4B (gift from Dr. Marco Conti) diluted at 1/10000; mouse antiPDE4D (gift from Dr Marco Conti) diluted at 1/1000 and rabbit anti- PDE3A (gift from Dr Chen Yan, University of Rochester, Rochester, NY) diluted at 1/10000.

Techniques: Over Expression, Injection, Luciferase, Virus, Staining, TUNEL Assay, Marker

Journal: Journal of the American Heart Association

Article Title: Cardiac Gene Therapy With Phosphodiesterase 2A Limits Remodeling and Arrhythmias in Mouse Models of Heart Failure

doi: 10.1161/jaha.124.037343

Figure Lengend Snippet: Figure 2. Gene therapy with PDE2A prevents cardiac remodeling and dysfunction induced by chronic isoproterenol infusion. A, Schematic representation of the experimental protocol. Mice were injected in the tail vein with 1012 viral particles of a serotype 9 adeno-associated viruses encoding for luciferase or phosphodiesterase 2A3. Fourteen days later, mice injected with AAV9-LUC were implanted subcutaneously with osmotic pumps diffusing either NaCl (NaCl-LUC) or isoproterenol at 60 mg/kg per day (isoproterenol- LUC) and animals injected with AAV9-PDE2A were implanted with pumps delivering isoproterenol at 60 mg/kg per day (isoproterenol- PDE2A). Treatment duration was 14 days (hatched bars). Minipumps were then removed and mice were kept for 2 additional weeks before euthanasia. Cardiac function was evaluated by serial echocardiography before injection of the virus as well as at 14, 28, 35, and 42 days. B, Left panel shows representative blots of PDE2A and vinculin. PDE2A protein expression in heart tissues extracts measured by Western blot and the bar graph represents the ratios of PDE2A over vinculin quantified expressed as mean±SEM in NaCl-LUC, isoproterenol-LUC and isoproterenol-PDE2A groups. C, Heart weight and lung weight over tibia length ratio expressed as mean±SEM. D, Time course of the normalized ratio of calculated left ventricular weight over body weight and normalized ejection fraction in NaCl-LUC, isoproterenol-LUC and isoproterenol-PDE2A mice. Number of mice is indicated in the brackets. E, Panel on the left, representative images of Masson’s trichrome staining (scale bar 100 μm), bar graph on the left represents quantifications of interstitial fibrosis as mean±SEM in NaCl-LUC (n=9), isoproterenol-LUC (n=9), and isoproterenol+PDE2A (n=9) groups. Statistical significance is indicated by the P value (* vs NaCl-LUC and † vs isoproterenol-LUC) determined using Welch’s t test (B), Kruskal– Wallis followed by a Dunn’s test (C panel bottom and E), 2-way ANOVA followed by a Tukey’s test (D), 1-way ANOVA followed by a Tukey’s test (C panel top). AAV9 indicates serotype 9 adeno-associated viruses; BW, body weight; HW, heart weight; Iso-LUC, isoproterenol-luciferase; Iso-PDE2A, isoproterenol-phosphodiesterase 2A; LUC, luciferase; LVW, left ventricular weight; LW, lung weight; PDE2A, phosphodiesterase 2A; and TL, tibia length.

Article Snippet: The primary antibodies used were as follows: (1) Figure 1: rabbit anti- PDE2A, Fabgennix; PDE2A- 101AP diluted at 1/1000; rabbit anti- GAPDH, Cell Signaling, 2118 diluted at 1/1000; (2) Figure 2: goat antiPDE2A, Santa Cruz, SC- 17228 diluted at 1/1000; mouse anti- vinculin, V9131 Sigma- Aldrich diluted at 1/1000; (3) Figure 3: rabbit anti- PDE2A, Fabgennix, PDE2A- 101AP diluted at 1/1000; rabbit anti- GAPDH, Cell Signaling, 2118 diluted at 1/1000; (4) Figure S1: rabbit anti- flag L5, Novus Biologicals, NBP1- 06712 diluted at 1/500; rabbit anti- GAPDH, Cell Signaling, 2118 diluted at 1/1000; rabbit anti- PDE2A, Proteintech, 55 306- 1- AP diluted at 1/1000; rabbit anti- flag L5, Novus Biologicals, NBP1- 06712 diluted at 1/500; rabbit anti- GAPDH, Cell Signaling, 2118 diluted at 1/1000; (5) Figure S2B: rabbit anti- PDE2A, Proteintech, 55 306- 1- AP diluted at 1/1000; (6) Figure S3: rabbit antiPDE2A, Proteintech, 55 306- 1- AP diluted at 1/1000; and (7) Figure S4: rabbit anti- PDE4A AC55 (gift from Dr. Marco Conti, University of California San Francisco, San Francisco, CA) diluted at 1/1000; rabbit anti- PDE4B (gift from Dr. Marco Conti) diluted at 1/10000; mouse antiPDE4D (gift from Dr Marco Conti) diluted at 1/1000 and rabbit anti- PDE3A (gift from Dr Chen Yan, University of Rochester, Rochester, NY) diluted at 1/10000.

Techniques: Injection, Luciferase, Virus, Expressing, Western Blot, Staining

Journal: Journal of the American Heart Association

Article Title: Cardiac Gene Therapy With Phosphodiesterase 2A Limits Remodeling and Arrhythmias in Mouse Models of Heart Failure

doi: 10.1161/jaha.124.037343

Figure Lengend Snippet: Figure 3. PDE2A overexpression limits maladaptive remodeling and cardiac dysfunction induced by chronic isoproterenol and phenylephrine infusion. A, Schematic representation of the experimental protocol. Mice were injected with 1012 viral particles of serotype 9 adeno-associated viruses encoding for Luciferase or phosphodiesterase 2A3. Fourteen days later, mice were implanted with osmotic minipumps diffusing either NaCl (NaCl-LUC) or isoproterenol+phenylephrine at 30 mg/kg per day each (isoproterenol+phenylephrine-LUC and isoproterenol + phenylephrine-PDE2A). Minipumps were removed 2 weeks later and mice were euthanized. Cardiac function was assessed throughout the protocol using echocardiography before the injection of the virus and at 2, 3, 4, and 6 weeks. B, Representative blots of PDE2A and GAPDH on the left panel are shown and the bar graph represents ratios of PDE2A over GAPDH quantifications expressed as mean±SEM in a subset of the animals treated with NaCl-LUC, isoproterenol+phenylephrine-LUC, and isoproterenol+phenylephrine-PDE2A. C, Heart weight and lung weight over tibia length ratios expressed as mean±SEM. D, Time course of the normalized ratios of calculated left ventricular weight (over body weight and normalized ejection fraction in NaCl-LUC, isoproterenol+phenylephrine-LUC, and isoproterenol+phenylephrine-PDE2A mice). Number of mice is indicated in the brackets. E, Top panel shows representative images of Masson’s trichrome staining (scale bar 200 μm), the middle panel depicts representative images of terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay (scale bar 100 μm) detecting apoptotic nuclei in green costained with the glycocalix marker wheat germ agglutinin in red and nuclei in blue colored with Hoechst. Bar graphs representing mean±SEM quantifications of interstitial fibrosis and apoptotic nuclei in NaCl-LUC (10), isoproterenol+phenylephrine- LUC (9) and isoproterenol+phenylephrine-PDE2A (9) mice are depicted. Statistical significance indicated by the P value (* vs NaCl- LUC and † vs isoproterenol+phenylephrine-LUC) was determined using Welch’s t test (B), Kruskal–Wallis followed by a Dunn’s test (C), 2-way ANOVA followed by a Tukey’s test (D), Welch’s 1-way ANOVA followed by a Dunnett’s test (E). AAV9 indicates serotype 9 adeno-associated viruses; BW, body weight; HW, heart weight; Iso-Phe-LUC, isoproterenol-phenylephrine-luciferase; Iso-Phe- PDE2A, isoproterenol-phenylephrine-phosphodiesterase 2A; LUC, luciferase; LVW, left ventricular weight; LW, lung weight; ns, not significant; PDE2A, phosphodiesterase 2A; and TL, tibia length.

Article Snippet: The primary antibodies used were as follows: (1) Figure 1: rabbit anti- PDE2A, Fabgennix; PDE2A- 101AP diluted at 1/1000; rabbit anti- GAPDH, Cell Signaling, 2118 diluted at 1/1000; (2) Figure 2: goat antiPDE2A, Santa Cruz, SC- 17228 diluted at 1/1000; mouse anti- vinculin, V9131 Sigma- Aldrich diluted at 1/1000; (3) Figure 3: rabbit anti- PDE2A, Fabgennix, PDE2A- 101AP diluted at 1/1000; rabbit anti- GAPDH, Cell Signaling, 2118 diluted at 1/1000; (4) Figure S1: rabbit anti- flag L5, Novus Biologicals, NBP1- 06712 diluted at 1/500; rabbit anti- GAPDH, Cell Signaling, 2118 diluted at 1/1000; rabbit anti- PDE2A, Proteintech, 55 306- 1- AP diluted at 1/1000; rabbit anti- flag L5, Novus Biologicals, NBP1- 06712 diluted at 1/500; rabbit anti- GAPDH, Cell Signaling, 2118 diluted at 1/1000; (5) Figure S2B: rabbit anti- PDE2A, Proteintech, 55 306- 1- AP diluted at 1/1000; (6) Figure S3: rabbit antiPDE2A, Proteintech, 55 306- 1- AP diluted at 1/1000; and (7) Figure S4: rabbit anti- PDE4A AC55 (gift from Dr. Marco Conti, University of California San Francisco, San Francisco, CA) diluted at 1/1000; rabbit anti- PDE4B (gift from Dr. Marco Conti) diluted at 1/10000; mouse antiPDE4D (gift from Dr Marco Conti) diluted at 1/1000 and rabbit anti- PDE3A (gift from Dr Chen Yan, University of Rochester, Rochester, NY) diluted at 1/10000.

Techniques: Over Expression, Injection, Luciferase, Virus, Staining, TUNEL Assay, Marker