cAMP-dependent protein kinase catalytic subunit PRKX; PrKX; protein kinase X; protein kinase X-linked; serine/threonine protein kinase PRKX; protein kinase PKX1 (PRKX, PKX1)

Function

• serine/threonine protein kinase regulated by & mediating cAMP signaling in cells
• acts through phosphorylation of downstream targets that may include CREB, SMAD6 & PKD1
• multiple functions in cellular differentiation & epithelial morphogenesis
• regulates myeloid cell differentiation through SMAD6 phosphorylation
• role in nephrogenesis by stimulating renal epithelial cell migration & tubulogenesis
• also involved in angiogenesis through stimulation of endothelial cell proliferation, migration & vascular-like structure formation
• binding of cAMP to PRKAR1A or PRKAR1B regulatory subunits induces dissociation of the holoenzyme heterotetramer
• released monomeric PRKX is then active & able to phosphorylate its substrates
• phosphorylated; autophosphorylates in vitro
• like other cAMP-dependent protein kinases, the inactive holoenzyme is probably composed of 2 PRKX catalytic subunits & a dimer of regulatory subunits
• interacts (cAMP-dependent) specifically with the regulatory subunits PRKAR1A & PRKAR1B
• compared to other cAMP-dependent Ser/Thr protein kinases, does not interact with the 2 other PKA regulatory subunits PRKAR2A & PRKAR2B
• interacts with cAMP-dependent protein kinase inhibitor/PKI proteins; inhibits PRKX
• interacts with GPKOW
  • interacts with SMAD6
• interacts with PKD1
• role in differentiation & controlled morphogenesis of the kidney
• interacts with PIN1 (via WW domain)

Kinetic parameters:

• KM=127 uM for ATP (in the presence of 10 mM Mg+2 chloride)
• KM=58 uM for kemptide (in the presence of 10 mM Mg+2 chloride)
• KM=6.7 uM for kemptide (in the presence of 1 uM Br-cAMP at 30 degrees C)

Structure

• 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

Compartment

• cytoplasm, nucleus
• cAMP induces nuclear translocation

Expression

• widely expressed (at protein level)
• specifically expressed in blood by macrophages & granulocytes
• expression is developmentally regulated, expressed in a wide range of developing tissues including liver, kidney, brain & pancreas (at protein level)
• induced by phorbol 12-myristate 13-acetate (PMA)

Pathology

• chromosomal translocation t(X;Y)(p22;p11) involving PRKX with PRKY is a cause of sex reversal disorder
• chromosomal translocations proximal to PRKY account for ~30% of cases of sex reversal disorder in XX males & XY females

More general terms

• serine/threonine kinase

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=5613
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:5613
• OMIM: https://mirror.omim.org/entry/300083
• UniProt: http://www.uniprot.org/uniprot/P51817.html