Dysbindin structural homologue CK1BP is an isoform-selective binding partner of human casein kinase-1.

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Yin H, Laguna KA, Li G, Kuret J

Dysbindin structural homologue CK1BP is an isoform-selective binding partner of human casein kinase-1.

Biochemistry. 2006 Apr 25;45(16):5297-308.

PubMed ID
16618118 [ View in PubMed
]
Abstract

Casein kinase-1 is a family of ubiquitous eukaryotic protein kinases that frequently function in tandem with the ubiquitin modification system to modulate protein turnover and trafficking. In Alzheimer's disease, these enzymes colocalize with ubiquitinated lesions, including neurofibrillary tangles and granulovacuolar degeneration bodies, suggesting they also play a role in disease pathogenesis. To identify binding partners that potentially regulate or recruit these enzymes toward disease lesions, a Sos-recruitment yeast two-hybrid screen was performed with human Ckidelta (the casein kinase-1 isoform most closely linked to granulovacuolar degeneration bodies) and a human brain cDNA library. All interacting clones contained a single open reading frame termed casein kinase-1 binding protein (CK1BP). On the basis of sequence alignments, CK1BP was a structural homologue of the acidic domain of dysbindin, a component of the dystrophin-associated protein complex and the biogenesis of lysosome-related organelles complex-1. CK1BP interacted with full-length Ckidelta, the isolated Ckidelta catalytic domain, Ckigamma2, -gamma3, and -epsilon in the yeast two-hybrid system, and bound Ckidelta and -epsilon in pulldown assays but did not interact with Ckialpha. Interaction with the Ckidelta catalytic domain led to concentration-dependent inhibition of protein kinase activity in the presence of protein substrates tau and alpha-synuclein. Although intact dysbindin did not bind any CK1 isoform, deletion of its coiled-coil domain yielded a protein fragment that behaved much like CK1BP in two-hybrid screens. These data suggest that the acidic domain of dysbindin and its paralogs in humans may function to recruit casein kinase-1 isoforms to protein complexes involved in multiple biological functions.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
Casein kinase I isoform epsilonP49674Details