A unique phosphatidylinositol 4-phosphate 5-kinase is activated by ADP-ribosylation factor in Plasmodium falciparum
| Autor: | Quinton L. Fivelman, Shamshad Cockcroft, Paul W. Bowyer, David A. Baker, Alison Skippen, Werner Leber |
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| Rok vydání: | 2009 |
| Předmět: |
Phosphatidylinositol 4-phosphate
Molecular Sequence Data Plasmodium falciparum Phosphatidylinositol Phosphates Protozoan Proteins Substrate Specificity chemistry.chemical_compound Animals Amino Acid Sequence Phosphatidylinositol biology ADP-Ribosylation Factors Kinase Phospholipase D Helix-Loop-Helix Motifs Protein Structure Tertiary Cell biology Pleckstrin homology domain Phosphotransferases (Alcohol Group Acceptor) Infectious Diseases Neuronal calcium sensor-1 chemistry Biochemistry biology.protein Parasitology Sequence Alignment Phosphoinositide-dependent kinase-1 |
| Zdroj: | International Journal for Parasitology. 39:645-653 |
| ISSN: | 0020-7519 |
| DOI: | 10.1016/j.ijpara.2008.11.015 |
| Popis: | In eukaryotes, calcium signalling has been linked to hydrolysis of the phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P(2)). The final enzyme in the synthesis of this phosphoinositide, a Type I phosphatidylinositol 4-phosphate 5-kinase (PIP5K), is activated by the small G protein ADP-ribosylation factor 1 (ARF1). In mammals, the ARF-PIP5K pathway is a key regulator of cell motility, secretion and cell signalling. We report the characterisation of a unique, putative bifunctional PIP5K in the human malaria parasite Plasmodium falciparum. The protein comprises a C-terminal, functional PIP5K domain with catalytic specificity for phosphatidylinositol 4-phosphate. The recombinant enzyme is activated by ARF1 but not phosphatidic acid. The protein also incorporates an unusual N-terminal domain with potential helix-loop-helix EF-hand-like motifs that is a member of the neuronal calcium sensor family (NCS). Intriguingly, NCS-1 has been shown to stimulate phosphatidylinositol 4-phosphate synthesis by activating mammalian and yeast phosphatidylinositol 4-kinase beta in vitro in a calcium-dependent manner. The unexpected physical attachment of an NCS-like domain to the plasmodial PIP5K might reflect a unique functional link between the calcium and PtdIns(4,5)P(2) pathways allowing modulation of PtdIns(4,5)P(2) production in response to changes in intracellular calcium concentrations within the parasite. |
| Databáze: | OpenAIRE |
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