Related Experiment Video

Updated: Aug 14, 2026

Genome-wide Analysis of HDAC Inhibitor-mediated Modulation of microRNAs and mRNAs in B Cells Induced to Undergo Class-switch DNA Recombination and Plasma Cell Differentiation
11:06

Genome-wide Analysis of HDAC Inhibitor-mediated Modulation of microRNAs and mRNAs in B Cells Induced to Undergo Class-switch DNA Recombination and Plasma Cell Differentiation

Published on: September 20, 2017

Protein kinase D1 phosphorylates HDAC7 and induces its nuclear export after T-cell receptor activation

Maribel Parra1, Herbert Kasler, Timothy A McKinsey

  • 1Gladstone Institute of Virology and Immunology, University of California, San Francisco, California 94158, USA.

The Journal of Biological Chemistry
|December 30, 2004
PubMed

Insights

Protein kinase D1 (PKD1) activation during T-cell receptor (TCR) signaling triggers the export of histone deacetylase 7 (HDAC7) from the nucleus. This process regulates Nur77 gene expression in thymocytes.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Biology

Background:

  • Histone deacetylase 7 (HDAC7) is highly expressed in thymocytes and inhibits T-cell receptor (TCR)-induced Nur77 transcription and apoptosis.
  • Understanding the regulation of HDAC7 localization and its role in thymocyte activation is crucial for immune response studies.

Purpose of the Study:

  • To investigate the signaling pathway regulating HDAC7 nuclear export upon TCR activation.
  • To elucidate the role of Protein kinase D1 (PKD1) in controlling HDAC7 localization and Nur77 expression.

Main Methods:

  • Utilized T-cell receptor (TCR) activation in thymocytes.
  • Employed biochemical assays to detect protein interactions and phosphorylation.
  • Performed site-directed mutagenesis to assess the role of specific serine residues in HDAC7.
  • Analyzed gene expression of Nur77 and observed thymocyte negative selection in a mouse model.

Main Results:

  • TCR activation induced calcium-independent export of HDAC7 from the nucleus to the cytoplasm.
  • PKD1 was activated by TCR engagement and phosphorylated HDAC7 at Ser155, Ser318, and Ser448, promoting its nuclear export.
  • Mutating these serine residues or inhibiting PKD1 activity blocked HDAC7 nucleocytoplasmic shuttling.
  • PKD1 activation led to transcriptional activation of Nur77, and PKD1 was active during thymocyte activation in vivo.

Conclusions:

  • PKD1 regulates HDAC7 nucleocytoplasmic shuttling through phosphorylation in response to TCR activation.
  • PKD1-mediated regulation of HDAC7 contributes to the control of Nur77 expression during thymocyte activation.
  • These findings reveal a novel mechanism controlling gene expression and apoptosis in developing T cells.

More Related Videos

Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay12:26

Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay

Published on: May 3, 2018

Co-immunoprecipitation Assay for Studying Functional Interactions Between Receptors and Enzymes09:40

Co-immunoprecipitation Assay for Studying Functional Interactions Between Receptors and Enzymes

Published on: September 28, 2018

Related Concept Videos

Amplifying Signals via Enzymatic Cascade01:22

Amplifying Signals via Enzymatic Cascade

When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze the...
Receptor Tyrosine Kinases01:26

Receptor Tyrosine Kinases

Receptor tyrosine kinases or RTKs are membrane-bound receptors that phosphorylate specific tyrosine on protein substrates. RTKs regulate cellular growth, differentiation, survival, and migration. They contain an extracellular ligand binding domain, a transmembrane domain, and a cytosolic tail with intrinsic kinase activity. Several extracellular signaling molecules activate RTKs in one or more ways and relay the signal downstream. Ligands such as platelet-derived growth factor (PDGF) or...
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...