Figure 8. Deduced schematic of coordination of phosphoproteome with transcriptome and proteome in cardiac-specific overexpression of adenylyl cyclase type 8 (TGAC8) mouse left ventricle (LV).

Based on our results, we deduced a mechanism of reprogramed phosphoproteome in TGAC8 mouse LV: First, TGAC8 mouse induces a PKA-dependent phosphorylation via AC8-cAMP-PKA axis. Many cytoplasmic proteins including transcription factors (TFs) are thus phosphorylated and then transported into the nuclear where TFs recognize and bind to the promotors to activate the transcription of more regulatory factors, including kinases, phosphatases, and TFs. The activation states of these factors are changed upon phosphorylated in the cytosol, thereby activating additional kinases-controlled phosphorylation cascades and reprogramming the cardiac phosphoproteome comprehensively. Left column: AC8-cAMP-PKA signaling; middle column: phosphorylation (phosphoproteome); lower right: transcription (transcriptome); upper right: translation (proteome).