A novel ERK-like, CRK-like protein kinase that modulates growth in Trypanosoma brucei via an autoregulatory C-terminal entension

J. Ellis, Mitali Sarkar, E. Hendriks, K. Matthews

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

The protozoan parasite Trypanosoma brucei undergoes a complex developmental cycle coordinated with cell cycle control. These processes in eukaryotes are frequently regulated through mitogen-activated protein kinases (MAPKs) and cyclin-dependent protein kinases (CDKs), respectively. We have discovered a novel protein kinase which shares features of both ERK-type MAPKs and CDKs (T. brucei ERK-like, CDK-like protein kinase). This molecule, named TbECK1, is similar to the unusual mammalian KKI-AMRE protein kinase family. Moreover, TbECK1 possesses a long C-terminal extension reminiscent of those found in mammalian ERK5, ERK7 and ERK8. Expression analyses demonstrate that TbECK1 is constitutively expressed during the trypanosome life cycle at both RNA and protein level. In transgenic parasites we demonstrate that expression of a mutant of TbECK1 that lacks the C-terminal extension produces a slow growth phenotype, associated with the appearance of cells with aberrant karyotypes. Using this as an assay we further demonstrate that the phenotype is dependent upon the potential for catalytic activity of TbECK1 and on the integrity of at least one of the phosphorylable amino acids in its phosphorylation lip. C-terminal extensions are a common feature of kinetoplastid protein kinases. Our results demonstrate for the first time that this domain has a regulatory function.
Original languageEnglish
Pages (from-to)1487-1499
Number of pages13
JournalMolecular Microbiology
Volume53
Issue number5
DOIs
Publication statusPublished - 2004

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