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Defective Anks1a disrupts the export of receptor tyrosine kinases from the endoplasmic reticulum
( Soochul Park ) 생화학분자생물학회 2016 BMB Reports Vol.49 No.12
EphA2 has been implicated in amplifying ErbB2 tumorigenic signaling. One protein that interacts with EphA2 is the Anks1a PTB adaptor. However, the precise role of Anks1a in EphA2- mediated tumorigenesis is unclear. We demonstrated that Anks1a localizes to the ER upon phosphorylation and that the Ankyrin repeats and PTB of Anks1a bind to EphA2 and Sec23, respectively. Thus, Anks1a facilitates the selective packaging of EphA2 into COPII vesicles. Additionally, Anks1a knockout mice, a phenocopy of EphA2 knockout mice, exhibited markedly reduced ErbB2-induced breast tumorigenesis. Strikingly, ErbB2 did not localize to the cell surface following Anks1a knockdown in primary mammary tumor cells over-expressing ErbB2. Importantly, EphA2 was critical for stabilizing ErbB2 through complex formation, but its interaction with Anks1a also facilitated ErbB2 loading into COPII carriers. These findings suggest a novel role for Anks1a in the molecular pathogenesis of breast tumors and possibly other human diseases. [BMB Reports 2016; 49(12): 651-652]
In Vivo Expression of the PTB-deleted Odin Mutant Results in Hydrocephalus
Park, Sunjung,Lee, Haeryung,Park, Soochul Korean Society for Molecular and Cellular Biology 2015 Molecules and cells Vol.38 No.5
Odin has been implicated in the downstream signaling pathway of receptor tyrosine kinases, such as the epidermal growth factor and Eph receptors. However, the physiologically relevant function of Odin needs to be further determined. In this study, we used Odin heterozygous mice to analyze the Odin expression pattern; the targeted allele contained a ${\beta}$-geo gene trap vector inserted into the 14t intron of the Odin gene. Interestingly, we found that Odin was exclusively expressed in ependymal cells along the brain ventricles. In particular, Odin was highly expressed in the subcommissural organ, a small ependymal glandular tissue. However, we did not observe any morphological abnormalities in the brain ventricles or ependymal cells of Odin null-mutant mice. We also generated BAC transgenic mice that expressed the PTB-deleted Odin (dPTB) after a floxed GFP-STOP cassette was excised by tissue-specific Cre expression. Strikingly, Odin-dPTB expression played a causative role in the development of the hydrocephalic phenotype, primarily in the midbrain. In addition, Odin-dPTB expression disrupted proper development of the subcommissural organ and interfered with ependymal cell maturation in the cerebral aqueduct. Taken together, our findings strongly suggest that Odin plays a role in the differentiation of ependymal cells during early postnatal brain development.
Soochul Park,노현아 한국분자세포생물학회 2016 Molecules and cells Vol.39 No.2
Eph receptors and their ligands, ephrins, mediate cell-to-cell contacts in a specific brain region and their bi-directional signaling is implicated in the regulation of apoptosis during early brain development. In this report, we used the alpha()-Cre transgenic line to induce ephrin-A5 over-expression in the distal region of the neural retina. Using this double transgenic embryo, we show that the over-expression of ephrin-A5 was responsible for inducing massive apoptosis in both the nasal and temporal retinas. In addition, the number of differentiated retinal neurons with the exception of the bipolar neuron was significantly reduced, whereas the laminar organization of the mature retina remained intact. Consistent with this finding, an analysis of the mature retina revealed that the size of the whole retina— particularly the nasal and temporal regions—is markedly reduced. These results strongly suggest that the level of ephrin-A5 expression plays a role in the regulation of the size of the retinal progenitor pool in the neural retina.
Properties of the Blends of Ethylene-Vinyl Acetate and Ethylene-$\alpha$-Olefins Copolymers
Park Soochul,Yim Chaiseok,Lee Byung H.,Choe Soonja The Polymer Society of Korea 2005 Macromolecular Research Vol.13 No.3
The effect of the vinyl acetate (VA) content on the thermal, viscoelastic, rheological, morphological and mechanical behaviors in various blends of ethylene-vinyl acetate (EVA)/ethylene-$\alpha$-olefin copolymers was investigated using 28, 22 and $15 mol\%$ of VA in EVA. In the DSC melting and crystallization thermograms of all of the EVA systems blended with ethylene-$\alpha$-olefin copolymers, discrete peaks were observed which were related to the constituents. In the dynamic mechanical thermal analysis, the storage modulus increased with increasing content of ethylene-$\alpha$-olefin copolymers. In addition, the transition regions relating to the tan bpeaks varied with the VA content. The crossover point between G' and G" varied depending on the VA contents, and shear-thinning was more prominent in the EVA/EtBC system. In the SEM investigation, a discrete phase morphology was observed in both the EVA/EtBC and EVA/EtOC blends, but the contrast improved with decreasing VA content. However, the tensile strength and modulus improved, but the elongation at break reduced with decreasing VA content, implying that the ethylene-$\alpha$-olefin copolymers play the role of reinforcing materials. Thus, the EVA and ethylene-$\alpha$-olefin components in the copolymers are immiscible in the molten and solid states, but are nevertheless mechanically compatible.
Park, Eunjeong,Noh, Hyuna,Park, Soochul Korean Society for Molecular and Cellular Biology 2017 Molecules and cells Vol.40 No.6
Ephrin-A5 has been implicated in the regulation of brain morphogenesis and axon pathfinding. In this study, we used bacterial homologous recombination to express a LacZ reporter in various ephrin-A5 BAC clones to identify elements that regulate ephrin-A5 gene expression during mesencephalon development. We found that there is mesencephalon-specific enhancer activity localized to a specific +25.0 kb to +30.5 kb genomic region in the first intron of ephrin-A5. Further comparative genomic analysis indicated that two evolutionary conserved regions, ECR1 and ECR2, were present within this 5.5 kb region. Deletion of ECR1 from the enhancer resulted in disrupted mesencephalon-specific enhancer activity in transgenic embryos. We also found a consensus binding site for basic helix-loop-helix (bHLH) transcription factors (TFs) in a highly conserved region at the 3'-end of ECR1. We further demonstrated that specific deletion of the bHLH TF binding site abrogated the mesencephalon-specific enhancer activity in transgenic embryos. Finally, both electrophoretic mobility shift assay and luciferase-based transactivation assay revealed that the transcription factor Ascl1 bound the bHLH consensus binding site in the mesencephalon-specific ephrin-A5 enhancer in vitro. Together, these results suggest that the bHLH TF binding site in ECR1 is involved in the positive regulation of ephrin-A5 gene expression during the development of the mesencephalon.
Soochul Park 한국통합생물학회 2004 Animal cells and systems Vol.8 No.1
This study provides evidence that expression of EphA8 receptor in NG108-15 cells results in a substantial increase in the number of neurite-bearing cells. However, the EphA8-induced neurite outgrowth does not require either ephrin-A5 stimulation or ectopic expression of p110g PI-3 kinase. In contrast, co-expression of a lipid kinase - inactive p110g mutant together with EphA8 causes neurite retraction in the presence of ephrin-A5 stimulation. This effect was not observed in the absence of ephrin-A5 stimulation. Significantly, the tyrosine kinase activity of EphA8 is not important for either of these processes. Taken together, our results strongly suggest that p110g PI-3 kinase is critically involved in the regulatory process by which ephrin-A5 exerts effects on the EphA8-induced neurite outgrowth.
Ependymal Cells Require Anks1a for Their Proper Development
Park, Sunjung,Lee, Haeryung,Lee, Jiyeon,Park, Eunjeong,Park, Soochul Korean Society for Molecular and Cellular Biology 2019 Molecules and cells Vol.42 No.3
Ependymal cells constitute the multi-ciliated epithelium, which lines the brain ventricular lumen. Although ependymal cells originate from radial glial cells in the perinatal rodent brain, the exact mechanisms underlying the full differentiation of ependymal cells are poorly understood. In this report, we present evidence that the Anks1a phosphotyrosine binding domain (PTB) adaptor is required for the proper development of ependymal cells in the rodent postnatal brain. Anks1a gene trap targeted LacZ reporter analysis revealed that Anks1a is expressed prominently in the ventricular region of the early postnatal brain and that its expression is restricted to mature ependymal cells during postnatal brain development. In addition, Anks1a-deficient ependymal cells were shown to possess type B cell characteristics, suggesting that ependymal cells require Anks1a in order to be fully differentiated. Finally, Anks1a overexpression in the lateral wall of the neonatal brain resulted in an increase in the number of ependymal cells during postnatal brain development. Altogether, our results suggest that ependymal cells require Anks1a PTB adaptor for their proper development.