INTRAMOLECULAR MASKING OF NUCLEAR IMPORT SIGNAL ON NF-AT4 BY CASEIN KINASE-I AND MEKK1

T cell activation requires the import of NF-AT transcription factors t o the nucleus, a process promoted by calcineurin-dependent dephosphory lation and inhibited by poorly understood protein kinases. Here, we re port the identification of two protein kinases that oppose NF-AT4 nucl ear import. Casein kinase I alpha directly binds and phosphorylates NF -AT4, resulting in the inhibiton of NF-AT4 nuclear translocation. MEKK 1 indirectly suppresses NF-AT4 nuclear import by stabilizing the inter action between NF-AT4 and CKI alpha. CKI alpha thus acts to establish an intramolecular masking of the nuclear location signal on NF-AT4, wh ile MEKK1 augments this mechanism, and may further provide a link to s ignal transduction pathways regulating NF-AT4.