UMMS Affiliation

Howard Hughes Medical Institute, Program in Molecular Medicine

Date

6-24-2000

Document Type

Article

Subjects

Amino Acid Motifs; Amino Acid Sequence; Animals; Calcineurin; Carrier Proteins; Cell Nucleus; DNA-Binding Proteins; Humans; Ionomycin; JNK Mitogen-Activated Protein Kinases; Jurkat Cells; *Karyopherins; Mitogen-Activated Protein Kinases; Molecular Sequence Data; Mutation; NFATC Transcription Factors; *Nuclear Proteins; Phosphorylation; *Receptors, Cytoplasmic and Nuclear; Recombinant Fusion Proteins; Signal Transduction; Tetradecanoylphorbol Acetate; Transcription Factors; Transcription, Genetic

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

The protein phosphatase calcineurin is a critical mediator of calcium signals during T-cell activation. One substrate of calcineurin is the transcription factor NFATc1, which is retained in the cytoplasm of quiescent cells. NFATc1 activation requires the translocation of the transcription factor into the nucleus, a process that is mediated by calcineurin. This interaction with calcineurin requires a targeting domain (PxIxIT motif) located in the NH(2)-terminal region of NFATc1. Here we demonstrate that the calcineurin targeting domain of NFATc1 is phosphorylated and inactivated by the c-Jun NH(2)-terminal kinase (JNK). This disruption of calcineurin targeting inhibits the nuclear accumulation and transcription activity of NFATc1 and accounts for the observation that Jnk1(-/-) T cells exhibit greatly increased NFATc1-dependent nuclear responses.

Rights and Permissions

Citation: Mol Cell Biol. 2000 Jul;20(14):5227-34.

Related Resources

Link to Article in PubMed

Journal Title

Molecular and cellular biology

PubMed ID

10866678

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