Tau-tubulin kinase 2

Definition:

Serine/threonine kinase that acts as a key regulator of ciliogenesis: controls the initiation of ciliogenesis by binding to the distal end of the basal body and promoting the removal of CCP110, which caps the mother centriole, leading to the recruitment of IFT proteins, which build the ciliary axoneme. Has some substrate preference for proteins that are already phosphorylated on a Tyr residue at the +2 position relative to the phosphorylation site. Able to phosphorylate tau on serines in vitro. Phosphorylates MPHOSPH9 which promotes its ubiquitination and proteasomal degradation, loss of MPHOSPH9 facilitates the removal of the CP110-CEP97 complex (a negative regulator of ciliogenesis) from the mother centrioles, promoting the initiation of ciliogenesis.

References:

[1]. Sarah C Goetz, et al. The spinocerebellar ataxia-associated gene Tau tubulin kinase 2 controls the initiation of ciliogenesis. Cell. 2012 Nov 9;151(4):847-858. [Content Brief]

[2]. Ning Huang, et al. M-Phase Phosphoprotein 9 regulates ciliogenesis by modulating CP110-CEP97 complex localization at the mother centriole. Nat Commun. 2018 Oct 30;9(1):4511. [Content Brief]

[3]. Michale Bouskila, et al. TTBK2 kinase substrate specificity and the impact of spinocerebellar-ataxia-causing mutations on expression, activity, localization and development. Biochem J. 2011 Jul 1;437(1):157-67. [Content Brief]

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