PKA/PRKACA Protein, Canine (His)

PKA/PRKACA is a kinase that phosphorylates a large number of substrates in the cytoplasm and nucleus (by similarity). It phosphorylates CDC25B, ABL1, NFKB1, CLDN3, PSMC5/RPT6, PJA2, RYR2, RORA, SOX9, and VASP (by similarity). By phosphorylating PJA2, PKA/PRKACA regulates the abundance of its regulatory subunits, as PJA2 binds and ubiquitinates these subunits, leading to their proteolysis. RORA is activated through phosphorylation. It plays a critical role in glucose-mediated adipogenic differentiation increase and osteogenic differentiation inhibition in osteoblasts (by similarity). It contributes to chondrogenesis by mediating SOX9 phosphorylation (by similarity). In platelet regulation, PKA/PRKACA maintains platelets in a resting state by phosphorylating inhibitory pathway proteins when complexed with NF-kappa-B (NFKB1 and NFKB2) and I-kappa-B-alpha (NFKBIA). However, thrombin and collagen disrupt these complexes, releasing active PRKACA, which stimulates platelets and promotes aggregation via VASP phosphorylation. RYR2 channel activity is enhanced by phosphorylation in the presence of luminal Ca²⁺, reducing the amplitude but increasing the frequency of store overload-induced Ca²⁺ release (SOICR), characterized by faster Ca²⁺ release and Ca²⁺ wave propagation despite lower wave amplitude and resting cytosolic Ca²⁺. PSMC5/RPT6 phosphorylation activates the proteasome. It negatively regulates tight junctions (TJs) in ovarian cancer cells via CLDN3 phosphorylation. NFKB1 phosphorylation promotes NF-kappa-B p50-p50 DNA binding. PKA/PRKACA inhibits GLI transcription factors via phosphorylation, preventing Hedgehog signaling target gene activation (by similarity). GLI phosphorylation is suppressed when PRKACA interacts with SMO, sequestering PRKACA at the membrane (by similarity). It regulates embryonic development by downregulating Hedgehog (Hh) signaling, likely through OFD1 in ciliogenesis (by similarity). It prevents meiosis resumption in prophase-arrested oocytes by inactivating CDC25B via phosphorylation (by similarity). It may also modulate rapid eye movement (REM) sleep in the pedunculopontine tegmental (PPT) (by similarity). Additionally, PKA/PRKACA phosphorylates APOBEC3G and AICDA and enhances HSF1 nuclear localization and transcriptional activity upon heat shock (by similarity). It acts as a negative regulator of mTORC1 by phosphorylating RPTOR (by similarity).