Intramolecular masking of nuclear import signal on NF-AT4 by casein kinase I and MEKK1

Cell. 1998 May 29;93(5):851-61. doi: 10.1016/s0092-8674(00)81445-2.

Abstract

T cell activation requires the import of NF-AT transcription factors to the nucleus, a process promoted by calcineurin-dependent dephosphorylation and inhibited by poorly understood protein kinases. Here, we report the identification of two protein kinases that oppose NF-AT4 nuclear import. Casein kinase Ialpha directly binds and phosphorylates NF-AT4, resulting in the inhibiton of NF-AT4 nuclear translocation. MEKK1 indirectly suppresses NF-AT4 nuclear import by stabilizing the interaction between NF-AT4 and CKIalpha. CKIalpha thus acts to establish an intramolecular masking of the nuclear location signal on NF-AT4, while MEKK1 augments this mechanism, and may further provide a link to signal transduction pathways regulating NF-AT4.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Biological Transport
  • Blotting, Western
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism
  • Casein Kinases
  • Cell Nucleus / metabolism
  • Cells, Cultured
  • Chromatography, Affinity
  • Culture Media, Serum-Free
  • DNA-Binding Proteins / metabolism*
  • Fluorescent Antibody Technique
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinases*
  • Models, Biological
  • Molecular Sequence Data
  • NFATC Transcription Factors
  • Nuclear Localization Signals*
  • Nuclear Proteins*
  • Phosphorylation
  • Precipitin Tests
  • Protein Binding
  • Protein Kinases / genetics
  • Protein Kinases / isolation & purification
  • Protein Kinases / metabolism*
  • Protein-Serine-Threonine Kinases / antagonists & inhibitors
  • Protein-Serine-Threonine Kinases / isolation & purification
  • Protein-Serine-Threonine Kinases / metabolism*
  • Protein-Tyrosine Kinases / antagonists & inhibitors
  • Protein-Tyrosine Kinases / isolation & purification
  • Protein-Tyrosine Kinases / metabolism*
  • Signal Transduction
  • Transcription Factors / metabolism*

Substances

  • Culture Media, Serum-Free
  • DNA-Binding Proteins
  • NFATC Transcription Factors
  • Nuclear Localization Signals
  • Nuclear Proteins
  • Transcription Factors
  • Protein Kinases
  • Protein-Tyrosine Kinases
  • Casein Kinases
  • Protein-Serine-Threonine Kinases
  • Calcium-Calmodulin-Dependent Protein Kinases
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinases