Protein Kinase X: A Novel Human Protein Kinase closely related to the Catalytic Subunit of cAMP-dependent Protein Kinase

Abstract

The recently isolated gene PRKX encodes a novel type of human protein kinase closely related to the cAMP-dependent protein kinase (cAPK). The hydrophilic protein of about 41 kDa is called Protein Kinase X (Prkx) because the gene is located on the short arm of the human X-chromosome (Klink et al. 1995). It has a striking sequence similarity to the DC2 protein kinase from Drosophila melanogaster (62.3% identity in the conserved catalytic core region) and has a lower similarity to the catalytic subunits of lower organisms like that of Ascaris suum (53.5% identity) and Caenorhabditis elegans (51.1%). These protein kinases differ from the “classical” CAMP-dependent protein kinases (cAPKs) by their isoelectric points and the lengths of their branches in the phylogenetic tree (table 1, figure 1). Most residues important for substrate recognition and binding of the regulatory subunits RI and RII are identical comparing the catalytic subunit of cAMP-dependent protein kinase alpha (Adams and Taylor 1993; Grant et a1.1996) and Protein Kinase X. The core region of the kinase is also highly conserved whereas the N-terminus is totally different. The N-terminus of Protein Kinase X contains a putative binding motif for WW-domains, which is a proline-rich region called PY-motif (Macias et al. 1996), that might be important for regulation or subcellular localization. Northern blot analysis with different subfragments, of cDNA clones indicates a widespread expression with the highest level of expression observed in fetal and adult brain, kidney and lung and low levels of expression in all other tested tissues (Klink et al. 1995). Prkx was expressed in E. coli using several different expression systems.