| First Author | Lin C | Year | 2005 |
| Journal | Hum Mol Genet | Volume | 14 |
| Issue | 24 | Pages | 3775-86 |
| PubMed ID | 16330482 | Mgi Jnum | J:106806 |
| Mgi Id | MGI:3619624 | Doi | 10.1093/hmg/ddi391 |
| Citation | Lin C, et al. (2005) CDKL5/Stk9 kinase inactivation is associated with neuronal developmental disorders. Hum Mol Genet 14(24):3775-86 |
| abstractText | X-linked cyclin-dependent kinase-like 5 (CDKL5 or STK9) has recently been implicated in atypical Rett and X-linked West syndromes, severe neurological disorders associated with mental retardation, loss of communication and motor skills and infantile spasms and seizures in predominantly females. Besides CDKL5, these disease phenotypes are also linked to mutations in the MECP2 and ARX genes. Here, we have expressed and characterized CDKL5 and its mutant forms. CDKL5 is a 118 kDa protein that is widely distributed in all tissues, with highest levels in brain, thymus and testes. Whole mount embryo staining reveals CDKL5 to be ubiquitous. Within cells, CDKL5 is localized primarily in the nucleus. Removal of the C-terminal domain increases CDKL5 expression, enhances autophosphorylation activity and causes perinuclear localization, indicating that the C-terminus regulates CDKL5 function. Although we detect MeCP2 but not ARX binding to CDKL5, our results suggest that neither of these proteins are direct substrates of the CDKL5 kinase. Finally, the CDKL5 mutations associated with the disease phenotype cause loss of kinase activity as assessed by autophosphorylation. These results suggest that inactivation of the CDKL5 kinase can lead to severe neurodevelopmental disorders. |
