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van Vlimmeren, A.

Publications and source records attributed to van Vlimmeren, A..

2 recordsLinked to original sources

Timing the origin of eukaryotic cellular complexity with ancient duplications

Eukaryogenesis is one of the most enigmatic evolutionary transitions, during which simple prokaryotic cells gave rise to complex eukaryotic cells. While evolutionary intermediates are lacking, gene duplications allow us to elucidate the order of events by which eukaryotes originated. Here we use a phylogenomics approach to reconstruct successive steps during eukaryogenesis. We found that gene duplications roughly doubled the proto-eukaryotic genome, with families inherited from the Asgard archaea-related host being duplicated most. By relatively timing events using phylogenetic distances we inferred that duplications in cytoskeletal and membrane trafficking families were among the earliest events, whereas most other families expanded primarily after mitochondrial endosymbiosis. Altogether, we demonstrate that the host that engulfed the proto-mitochondrion had some eukaryote-like complexity, which further increased drastically upon mitochondrial acquisition. This scenario bridges the signs of complexity observed in Asgard archaeal genomes to the proposed role of mitochondria in triggering eukaryogenesis.

evolutionary biology↗

Comprehensive substrate specificity profiling of the human nek kinome reveals unexpected signaling outputs

Human NimA-related kinases (Neks) have multiple mitotic and non-mitotic functions, but few substrates are known. We systematically determined the phosphorylation-site motifs for the entire Nek kinase family, except for Nek11. While all Nek kinases strongly select for hydrophobic residues in the -3 position, the family separates into four distinct groups based on specificity for a serine versus threonine phospho-acceptor, and preference for basic or acidic residues in other positions. Unlike Nek1-Nek9, Nek10 is a dual-specificity kinase that efficiently phosphorylates itself and peptide substrates on serine and tyrosine, and its activity is enhanced by tyrosine auto-phosphorylation. Nek10 dual-specificity depends on residues in the HRD+2 and APE-4 positions that are uncommon in either serine/threonine or tyrosine kinases. Finally, we show that the phosphorylation-site motifs for the mitotic kinases Nek6, Nek7 and Nek9 are essentially identical to that of their upstream activator Plk1, suggesting that Nek6/7/9 function as phospho-motif amplifiers of Plk1 signaling.

biochemistry↗