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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 [2] - 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

General

serine/threonine kinase

Properties

SIZE: entity length = 358 aa MW = 41 kD COMPARTMENT: cytoplasm cell nucleus STATE: active state MOTIF: kinase domain SITE: 49-303 MOTIF: ATP-binding site NAME: ATP-binding site SITE: 55-63 ATP-binding site NAME: ATP-binding site SITE: 78-78 aspartate residue {D172} S/T phosphorylation site AGC-kinase C-terminal {304-358}

Database Correlations

OMIM 300083 UniProt P51817 Pfam PF00069 Entrez Gene 5613 Kegg hsa:5613 ENZYME 2.7.11.1

References

  1. UniProt :accession P51817
  2. Semizarov D et al A lineage-specific protein kinase crucial for myeloid maturation. Proc Natl Acad Sci U S A. 1998 Dec 22;95(26):15412-7. PMID: 9860982