Biomedical subjects

Hsiu-Cheng Hung

Publications and source records attributed to Hsiu-Cheng Hung.

5 recordsLinked to original sources

PubMed2006

Role of the T cell receptor alpha chain in the development and phenotype of naturally arising CD4+CD25+ T cells.

The T cell receptor alpha chain repertoire and the possible influence of the alpha chain on the development and phenotype of naturally arising mouse CD4+CD25+ T cells have not been extensively analysed. We used all available Valpha-specific monoclonal antibodies and a sensitive multiplex genomic DNA PCR assay to study the Valpha repertoire of CD4+CD25+ T cells in normal mice. To address whether CD4+CD25+ T cells express two TCR alpha chains, we have carried out four-colour flow cytometry using combinations of the available anti-Valpha reagents in mice where one allele of the TCRA locus had been inactivated. Results indicate that the Valpha repertoire of CD4+CD25+ T cells is as diverse as their CD25- partners. In addition, CD4+CD25+ T cells develop normally in Tcralpha+/- mice and we show for the first time that despite expressing only one TCRalpha chain, they retain their characteristic CD4(low), CD3(low), TCRbeta(low), CD5(high), CD45RB(low) and cytoplasmic CD152(high) phenotype.

Animals↗

PubMed2006

Second messenger and Ras/MAPK signalling pathways regulate CLOCK/CYCLE-dependent transcription.

The heterodimeric complex of the transcription factors CLOCK (CLK) and CYCLE (CYC) constitutes the positive element of the circadian clock in Drosophila and mammals. Phosphorylation of clock proteins represents an essential mechanism for promotion and control of the molecular oscillator. However, the kinases and signalling pathways that regulate CLK/CYC function remain largely elusive. In the present study we performed a chemical screen of kinase inhibitors in a cell culture reporter assay to identify functional regulators of CLK/CYC-dependent gene expression. These studies and analysis of constitutively active forms of kinases revealed that cyclic nucleotide/protein kinase A (PKA), calcium/calmodulin-dependent kinase (CaMK) II and Ras/mitogen-activated protein kinase (MAPK) regulate CLK/CYC activity. In vitro phosphorylation analysis showed a direct phosphorylation of CLK by CaMK II and p42 MAPK [extracellular signal-regulated kinase (ERK) 2], suggesting that these kinases regulate CLK/CYC-dependent transcription by direct phosphorylation of CLK.

ARNTL Transcription Factors↗

PubMed2003

Syndecan captures, protects, and transmits HIV to T lymphocytes.

This study demonstrates that syndecan functions as an in trans HIV receptor. We show that syndecan, when expressed in nonpermissive cells, becomes the major mediator for HIV adsorption. This adsorption is mediated by the binding of gp120 to the heparan sulfate chains of syndecan. Although syndecan does not substitute for HIV entry receptors, it enhances the in trans infectivity of a broad range of primate lentiviruses including primary viruses produced from PBMCs. Furthermore, syndecan preserves virus infectivity for a week, whereas unbound virus loses its infectivity in less than a day. Moreover, we obtain evidence suggesting that the vast syndecan-rich endothelial lining of the vasculature can provide a microenvironment which boosts HIV replication in T cells.

Animals↗

PubMed2002

Active site residues of cyclophilin A are crucial for its signaling activity via CD147.

Cyclophilin A (CyPA), a ubiquitously distributed intracellular protein, is a peptidylprolyl cis-trans-isomerase and the major target of the potent immunosuppressive drug cyclosporin A. Although expressed predominantly as an intracellular molecule, CyPA is secreted by cells in response to inflammatory stimuli and is a potent neutrophil and eosinophil chemoattractant in vitro and in vivo. The mechanisms underlying CyPA-mediated signaling and chemotaxis are unknown. Here, we identified CD147 as a cell surface receptor for CyPA and demonstrated that CD147 is an essential component in the CyPA-initiated signaling cascade that culminates in ERK activation. Both signaling and chemotactic activities of CyPA depended also on the presence of heparans, which served as primary binding sites for CyPA on target cells. The proline 180 and glycine 181 residues in the extracellular domain of CD147 were critical for signaling and chemotactic activities mediated by CD147. Also crucial were active site residues of CyPA, because rotamase-defective CyPA mutants failed to initiate signaling events. These results establish cyclophilins as natural ligands for CD147 and suggest an unusual, rotamase-dependent mechanism of signaling.

Amino Acid Sequence↗

PubMed2001

Functional equivalence of late gene promoters in bean golden mosaic virus with those in tomato golden mosaic virus.

In the bipartite geminivirus tomato golden mosaic virus (TGMV), the activity of late gene promoters is up-regulated by the multifunctional viral protein AL2. Cis-acting sequences required for AL2-mediated promoter responses have not been well characterized. However, nucleotide sequence analysis has implicated a motif termed the conserved late element (CLE). The CLE is present in TGMV and many other begomoviruses, although it is not ubiquitous. Here we analysed the regulation of late gene expression in bean golden mosaic virus (BGMV), one of the begomoviruses which lacks the CLE. Transient reporter gene assays showed that BGMV late gene promoters were trans-activated in Nicotiana benthamiana protoplasts, both by the homologous BGMV AL2 protein and by the heterologous TGMV AL2 protein. The BGMV AL2 protein also trans-activated TGMV late gene promoters. Consistent with these results, we found that hybrid viruses with the late gene promoters exchanged between BGMV and TGMV were viable in planta.

DNA, Viral↗