Biomedical subjects

Hyung-Bae Kwon

Publications and source records attributed to Hyung-Bae Kwon.

3 recordsLinked to original sources

PubMed2004

Double-knockout mice for alpha- and beta-synucleins: effect on synaptic functions.

An abundant presynaptic protein, alpha-synuclein, is centrally involved in the pathogenesis of Parkinson's disease. However, conflicting data exist about the normal function of alpha-synuclein, possibly because alpha-synuclein is redundant with the very similar beta-synuclein. To investigate the functions of synucleins systematically, we have now generated single- and double-knockout (KO) mice that lack alpha- and/or beta-synuclein. We find that deletion of synucleins in mice does not impair basic brain functions or survival. We detected no significant changes in the ultrastructure of synuclein-deficient synapses, in short- or long-term synaptic plasticity, or in the pool size or replenishment of recycling synaptic vesicles. However, protein quantitations revealed that KO of synucleins caused selective changes in two small synaptic signaling proteins, complexins and 14-3-3 proteins. Moreover, we found that dopamine levels in the brains of double-KO but not single-KO mice were decreased by approximately 20%. In contrast, serotonin levels were unchanged, and dopamine uptake and release from isolated nerve terminals were normal. These results show that synucleins are not essential components of the basic machinery for neurotransmitter release but may contribute to the long-term regulation and/or maintenance of presynaptic function.

Animals↗

PubMed2002

Drosophila extracellular signal-regulated kinase involves the insulin-mediated proliferation of Schneider cells.

The Drosophila insulin pathway is involved in the control of the proliferation and size of the cell. The stimulation of Schneider cells with human insulin has been observed to activate Drosophila extracellular signal regulated kinase (DERK). However, the role of DERK in the regulation of proliferation is unknown. In this study, we have identified a role of DERK in the proliferation of Drosophila Schneider cells. The inhibition of DERK activity by the overexpression of DMKP-3, an ERK-specific mitogen-activated protein kinase (MAPK) phosphatase, inhibited G(1) to S phase cell cycle progression as well as bromodeoxyuridine (BrdU) incorporation, which were previously increased by human insulin. However, DMKP-3 overexpression did not significantly reduce cell size that was also enlarged by insulin treatment, which suggests the specificity of the ERK pathway in proliferation but not for cell size. G1 to S phase cell cycle progression and BrdU incorporation were also reduced by catalytically inactive DMKP-3 mutant, and they may be acquired by the trapping of DERK into cytosol. The depletion of DERK or DMKP-3 by inhibitory double-stranded RNA decreased and increased BrdU incorporation, respectively. Thus, we propose that DERK is involved in the proliferation of Schneider cells via the insulin pathway.

Animals↗

PubMed2002

Isolation and characterization of a Drosophila homologue of mitogen-activated protein kinase phosphatase-3 which has a high substrate specificity towards extracellular-signal-regulated kinase.

A partial C-terminal cDNA sequence of a novel Drosophila mitogen-activated protein kinase phosphatase (MKP), designated DMKP-3, was identified from an epitope expressed sequence tag database, and the missing N-terminal cDNA fragment was cloned from a Drosophila cDNA library. DMKP-3 is a protein of 411 amino acids, with a calculated molecular mass of 45.8 kDa; the deduced amino acid sequence is most similar to that of mammalian MKP-3. Recombinant DMKP-3 produced in Escherichia coli retained intrinsic tyrosine phosphatase activity. In addition, DMKP-3 specifically inhibited extracellular-signal-regulated kinase (ERK) activity, but was without a significant affect on c-Jun N-terminal kinase (JNK) and p38 activities, when it was overexpressed in Schneider cells. DMKP-3 interacted specifically with Drosophila ERK (DERK) via its N-terminal domain. In addition, DMKP-3 specifically inhibited Elk-1-dependent trans-reporter gene expression in mammalian CV1 cells, and dephosphorylated activated mammalian ERK in vitro. DMKP-3 is uniquely localized in the cytoplasm within Schneider cells, and gene expression is tightly regulated during development. Thus DMKP-3 is a Drosophila homologue of mammalian MKP-3, and may play important roles in the regulation of various developmental processes.

Amino Acid Sequence↗