Cyclin-Dependent Kinase-Like 5 (CDKL5): Possible Cellular Signalling Targets and Involvement in CDKL5 Deficiency Disorder

Figure 3

CDKL5 and phosphorylative signalling. Although CDKL5 is localised in both, the nucleus and the cytoplasm, its localisation is partly controlled by phosphorylation. Phosphorylation of CDKL5 by Dyrk1a results in its translocation to the cytoplasm. Dephosphorylation by PP1 stimulated by NMDA receptor-dependent signalling also induces strong accumulation of CDKL5 in the cytoplasm. Further, CDKL5 probably regulates its own activity via inter- and intramolecular autophosphorylation. MeCP2, Dnmt1, and HDAC4 are substrates of CDKL5, and their phosphorylation is predicted to transcriptionally regulate their control of gene expression. Finally, phosphorylation of Amph1 and NGL-1 may be involved in synapse formation and neurotransmission. Recently, phosphorylation of MAP1S has been shown to play an important role in its ability to bind to microtubules. cis: intramolecular autophosphorylation; trans: intermolecular autophosphorylation.