Ciliopathy-Associated Protein Kinase ICK Requires Its Non-Catalytic Carboxyl-Terminal Domain for Regulation of Ciliogenesis
| Autor: | Eric J. Wang, David L. Brautigan, Yoon Seon Oh, Benjamin L. Allen, Zheng Fu, Casey D. Gailey |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Kinesins Protein Serine-Threonine Kinases environment and public health Article Mice 03 medical and health sciences 0302 clinical medicine primary cilia Protein Domains and phosphorylation ciliopathy-associated protein kinase Ciliogenesis medicine Animals Humans KIF3A Cilia Phosphorylation Protein kinase A lcsh:QH301-705.5 Chemistry Cilium kinesin family member 3A intestinal cell kinase General Medicine medicine.disease Cell biology Ciliopathy HEK293 Cells 030104 developmental biology ciliopathy lcsh:Biology (General) NIH 3T3 Cells Kinesin CTD 030217 neurology & neurosurgery ciliogenesis |
| Zdroj: | Cells Volume 8 Issue 7 Cells, Vol 8, Iss 7, p 677 (2019) |
| ISSN: | 2073-4409 |
| DOI: | 10.3390/cells8070677 |
| Popis: | Loss-of-function mutations in the human ICK (intestinal cell kinase) gene cause dysfunctional primary cilia and perinatal lethality which are associated with human ciliopathies. The enzyme that we herein call CAPK (ciliopathy-associated protein kinase) is a serine/threonine protein kinase that has a highly conserved MAPK-like N-terminal catalytic domain and an unstructured C-terminal domain (CTD) whose functions are completely unknown. In this study, we demonstrate that truncation of the CTD impairs the ability of CAPK to interact with and phosphorylate its substrate, kinesin family member 3A (KIF3A). We also find that deletion of the CTD of CAPK compromises both localization to the primary cilium and negative regulation of ciliogenesis. Thus, CAPK substrate recognition, ciliary targeting, and ciliary function depend on the non-catalytic CTD of the protein which is predicted to be intrinsically disordered. |
| Databáze: | OpenAIRE |
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