Cytoplasmic localization of calcium/calmodulin-dependent protein kinase I-α depends on a nuclear export signal in its regulatory domain

Calcium/calmodulin-dependent protein kinase I-α (CaMKI-α) is a ubiquitous cytosolic enzyme that phosphorylates a number of nuclear proteins in vitro and has been implicated in transcriptional regulation. We report that cytoplasmic localization of CaMKI-α depends on CRM1-mediated nuclear export mediated through a Rev-like nuclear export signal in the CaMKI-α regulatory domain. Interaction of CaMKI-α with a CRM1 complex in vitro is enhanced by incubation with calcium/calmodulin. Translocation of CaMKI-α into the nucleus involves a conserved sequence located within the catalytic core. Mutation of this sequence partially blocks nuclear entry of an export-impaired mutant of CaMKI-α.