Function: Serine/threonine protein kinase regulated by and mediating cAMP signaling in cells. Acts through phosphorylation of downstream targets that may include CREB, SMAD6 and PKD1 and has multiple functions in cellular differentiation and epithelial morphogenesis. Regulates myeloid cell differentiation through SMAD6 phosphorylation. Involved in nephrogenesis by stimulating renal epithelial cell migration and tubulogenesis. Also involved in angiogenesis through stimulation of endothelial cell proliferation, migration and vascular-like structure formation. Ref.4 Ref.6 Ref.7 Ref.9 Ref.10 Ref.11 Ref.13
Catalytic activity: ATP + a protein = ADP + a phosphoprotein. Ref.5 Ref.6
Enzyme regulation: Binding of cAMP to the PRKAR1A or PRKAR1B regulatory subunits induces dissociation of the holoenzyme heterotetramer. The released monomeric PRKX is then active and able to phosphorylate its substrates. Ref.5 Ref.6 Ref.12
Subunit structure: Like other cAMP-dependent protein kinases, the inactive holoenzyme is probably composed of 2 PRKX catalytic subunits and a dimer of regulatory subunits. Interacts (cAMP-dependent) specifically with the regulatory subunits PRKAR1A and PRKAR1B. Compared to other cAMP-dependent serine/threonine protein kinases, does not interact with the 2 other PKA regulatory subunits PRKAR2A and PRKAR2B. Interacts with cAMP-dependent protein kinase inhibitor/PKI proteins; inhibits PRKX. Interacts with GPKOW. Interacts with SMAD6. Interacts with PKD1; involved in differentiation and controlled morphogenesis of the kidney. Interacts with PIN1 (via WW domain). Ref.5 Ref.9 Ref.10 Ref.11 Ref.12
Subcellular location: Cytoplasm. Nucleus. Note: cAMP induces nuclear translocation. Ref.5 Ref.6 Ref.9
Tissue specificity: Widely expressed (at protein level). Specifically expressed in blood by macrophages and granulocytes according to Ref.4. Ref.1 Ref.4 Ref.7 Ref.8
Developmental stage: Expression is developmentally regulated being high and specific in a wide range of developing tissues including liver, kidney, brain and pancreas (at protein level). Ref.6 Ref.7 Ref.8
Induction: Up-regulated by phorbol 12-myristate 13-acetate (PMA). Ref.4 Ref.5 Ref.6 Ref.9 Ref.12
Post-translational modification: Phosphorylated; autophosphorylates in vitro. Ref.5 Ref.9
Involvement in disease: A chromosomal aberration involving PRKX is a cause of sex reversal disorder. Translocation t(X;Y)(p22;p11) with PRKY. Chromosomal translocations proximal to PRKY account for about 30% of the cases of sex reversal disorder in XX males and XY females.
Sequence similarities: Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. cAMP subfamily.Contains 1 AGC-kinase C-terminal domain.Contains 1 protein kinase domain.
Biophysicochemical propertiesKinetic parameters:KM=127 µM for ATP (in the presence of 10 mM magnesium chloride) Ref.5 Ref.6KM=58 µM for kemptide (in the presence of 10 mM magnesium chloride)KM=6.7 µM for kemptide (in the presence of 1 µM Br-cAMP at 30 degrees Celsius)
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