Title

Activation of a Plasmodium falciparum cdc2-related kinase by heterologous p25 and cyclin H - Functional characterization of a P. falciparum cyclin homologue

Authors

Authors

K. Le Roch; C. Sestier; D. Dorin; N. Waters; B. Kappes; D. Chakrabarti; L. Meijer;C. Doerig

Comments

Authors: contact us about adding a copy of your work at STARS@ucf.edu

Abbreviated Journal Title

J. Biol. Chem.

Keywords

PROTEIN-KINASE; DEPENDENT KINASE-5; CELL-CYCLE; MECHANISMS; INHIBITORS; EXPRESSION; PHOSPHORYLATION; CLONING; CDK5; CAK; Biochemistry & Molecular Biology

Abstract

Several Plasmodium falciparum genes encoding cdc2-related protein kinases have been identified, but the modalities of their regulation remains largely unexplored. Zn the present study, we investigated the regulation in vitro of PfPK5, a putative homologue of Cdk1 (cdc2) in P. falciparum. We show that (i) PfPK5 is efficiently activated by heterologous (human) cyclin H and p25, a cyclin-like molecule that specifically activates human Cdk5; (ii) the activated enzyme can be inhibited by chemical Cdk inhibitors; (iii) Pfmrk, a putative P. falciparum homologue of the Cdk-activating kinase, does neither activate nor phosphorylate PfPK5; and (iv) PfPK5 is able to autophosphorylate in the presence of a cyclin, Taken together, these results suggest that the regulation of Plasmodium Cdks may differ in important aspects from that of their human counterparts. Furthermore, we cloned an open reading frame encoding a novel P. falciparum protein possessing maximal homology to cyclin H from various organisms, and we show that this protein, called Pfcyc-1, is able to activate recombinant PfPK5 in vitro with an efficiency similar to that of human cyclin H and p25, This work opens the way to the development of screening procedures aimed at identifying compounds that specifically target the parasite Cdks.

Journal Title

Journal of Biological Chemistry

Volume

275

Issue/Number

12

Publication Date

1-1-2000

Document Type

Article

Language

English

First Page

8952

Last Page

8958

WOS Identifier

WOS:000086507700093

ISSN

0021-9258

Share

COinS