%0 Journal Article
%T Post-translational generation of constitutively active cores from larger phosphatases in the malaria parasite, Plasmodium falciparum: implications for proteomics
%A Rajinder Kumar
%A Alla Musiyenko
%A Anja Oldenburg
%A Brian Adams
%A Sailen Barik
%J BMC Molecular Biology
%D 2004
%I BioMed Central
%R 10.1186/1471-2199-5-6
%X P. falciparum encodes a number of Ser/Thr protein phosphatases (PP) whose catalytic subunits are composed of a catalytic core and accessory domains essential for regulation of the catalytic activity. Two examples of such regulatory domains are found in the Ca+2-regulated phosphatases, PP7 and PP2B (calcineurin). The EF-hand domains of PP7 and the calmodulin-binding domain of PP2B are essential for stimulation of the phosphatase activity by Ca+2. We present biochemical evidence that P. falciparum generates these full-length phosphatases as well as their catalytic cores, most likely as intermediates of a proteolytic degradation pathway. While the full-length phosphatases are activated by Ca+2, the processed cores are constitutively active and either less responsive or unresponsive to Ca+2. The processing is extremely rapid, specific, and occurs in vivo.Post-translational cleavage efficiently degrades complex full-length phosphatases in P. falciparum. In the course of such degradation, enzymatically active catalytic cores are produced as relatively stable intermediates. The universality of such proteolysis in other phosphatases or other multi-domain proteins and its potential impact on the overall proteome of a cell merits further investigation.The cellular proteome, the end product in the flow of genetic information in biology [1], is generally well predicted from the genome sequence [2]. The initially translated polypeptides, however, may undergo a variety of post-translational modifications that must be determined experimentally [3,4]. A major post-translation event in the life of a protein is proteolytic processing [5]. Although proteolysis is undoubtedly responsible for the general degradation and turn over of all proteins, it often constitutes a physiologically important mechanism of biological regulation for specific proteins and pathways. Among the best studied examples are: the production of enzymes from zymogens (such as trypsin from trypsinogen) [6], generat
%U http://www.biomedcentral.com/1471-2199/5/6