• Title/Summary/Keyword: transmembrane protein

Search Result 287, Processing Time 0.029 seconds

Functional Analysis of the First Mannosyltransferase (PIG-M) involved in Glycosylphosphatidylinositol Synthesis in Plasmodium falciparum

  • Kim, Youn Uck;Hong, Yeongjin
    • Molecules and Cells
    • /
    • v.24 no.2
    • /
    • pp.294-300
    • /
    • 2007
  • The mammalian glycosylphosphatidylinositol (GPI) anchor consists of three mannoses attached to acylated GlcN-(acyl)PI to form $Man_3$-GlcN-(acyl)PI. The first of the three mannose groups is attached to an intermediate to generate Man-GlcN-(acyl)PI by the first mannosyltransferase (GPI-MT-I). Mammalian and protozoan GPI-MT-I have different substrate specificities. PIG-M encodes the mammalial GPI-MT-I which has 423 amino acids and multiple transmembrane domains. In this work we cloned PIG-M homologues from humans, Plasmodium falciparum (PfPIG-M), and Saccharomyces cerevisiae (GPI14), to test whether they could complement GPI-MT-I-deficient mammalian cells, since this biosynthetic step is likely to be a good target for selective screening of inhibitors against many pathogenic organisms. PfPIG-M partially restored cell surface expression of the GPI-anchored protein CD59 in PIG-M deficient mammalian cells, and first mannose transfer activity in vitro; however, this was not the case for GPI14.

Homology Modeling of CCR 4: Novel Therapeutic Target and Preferential Maker for Th2 Cells

  • Shalini, M.;Madhavan, Thirumurthy
    • Journal of Integrative Natural Science
    • /
    • v.7 no.4
    • /
    • pp.234-240
    • /
    • 2014
  • C-C chemokine receptor type 4 (CCR4) is a chemokine receptor with seven transmembrane helices and it belongs to the GPCR family. It plays an important role in asthma, lung disease, atopic dermatitis, allergic bronchopulmonary aspergillosis, cancer, inflammatory bowel disease, the mosquito-borne tropical diseases, such as dengue fever and allergic rhinitis. Because of its role in wide spectrum of disease processes, CCR4 is considered to be an important drug target. Three dimensional structure of the protein is essential to determine the functions. In the present study homology modeling of human CCR4 was performed based on crystal structure of CCR5 chemokine receptor. The generated models were validated using various parameters. Among the generated homology models the best one is selected based on validation result. The model can be used for performing further docking studies to identifying the critical interacting residues.

Upstream paths for Hippo signaling in Drosophila organ development

  • Choi, Kwang-Wook
    • BMB Reports
    • /
    • v.51 no.3
    • /
    • pp.134-142
    • /
    • 2018
  • Organ growth is fundamental to animal development. One of major mechanisms for growth control is mediated by the conserved Hippo signaling pathway initially identified in Drosophila. The core of this pathway in Drosophila consists of a cascade of protein kinases Hippo and Warts that negatively regulate transcriptional coactivator Yorkie (Yki). Activation of Yki promotes cell survival and proliferation to induce organ growth. A key issue in Hippo signaling is to understand how core kinase cascade is activated. Activation of Hippo kinase cascade is regulated in the upstream by at least two transmembrane proteins Crumbs and Fat that act in parallel. These membrane proteins interact with additional factors such as FERM-domain proteins Expanded and Merlin to modulate subcellular localization and function of the Hippo kinase cascade. Hippo signaling is also influenced by cytoskeletal networks and cell tension in epithelia of developing organs. These upstream events in the regulation of Hippo signaling are only partially understood. This review focuses on our current understanding of some upstream processes involved in Hippo signaling in developing Drosophila organs.

Apelin-APJ Signaling: a Potential Therapeutic Target for Pulmonary Arterial Hypertension

  • Kim, Jongmin
    • Molecules and Cells
    • /
    • v.37 no.3
    • /
    • pp.196-201
    • /
    • 2014
  • Pulmonary arterial hypertension (PAH) is a progressive disease characterized by the vascular remodeling of the pulmonary arterioles, including formation of plexiform and concentric lesions comprised of proliferative vascular cells. Clinically, PAH leads to increased pulmonary arterial pressure and subsequent right ventricular failure. Existing therapies have improved the outcome but mortality still remains exceedingly high. There is emerging evidence that the seven-transmembrane G-protein coupled receptor APJ and its cognate endogenous ligand apelin are important in the maintenance of pulmonary vascular homeostasis through the targeting of critical mediators, such as Kr$\ddot{u}$ppel-like factor 2 (KLF2), endothelial nitric oxide synthase (eNOS), and microRNAs (miRNAs). Disruption of this pathway plays a major part in the pathogenesis of PAH. Given its role in the maintenance of pulmonary vascular homeostasis, the apelin-APJ pathway is a potential target for PAH therapy. This review highlights the current state in the understanding of the apelin-APJ axis related to PAH and discusses the therapeutic potential of this signaling pathway as a novel paradigm of PAH therapy.

Chitosan surface grafted with fusion protein of FGF-2 and Fibronectin-FGF for tissue regeneration therapy

  • Hwang, Jeong-Hyo;Lee, Jue-Yeon;Kim, Sun-Chul;Jang, Jun-Hyeog;Ku , Young;Chung, Chong-Pyoung;Lee, Seung-Jin
    • Proceedings of the PSK Conference
    • /
    • 2003.10b
    • /
    • pp.231.3-232
    • /
    • 2003
  • The biomedical applications of chitosan have been widely researched. FN mediates its biological effects through binding to the hetero-dimeric transmembrane glycoproteins, integrins, which physically couple the cytoskeleton to the ECM. FN binds to the integrin through a consensus site including the Arg-Gly-Asp (RGD) sequence within tenth type III module (Ruoslahti & Pierschbacher 1987). A short sequence Pro-His-Ser-Arg-Asn (PHSRN) has also been identified as a synergistic motif within ninth type III module for binding to ${\alpha}$5${\beta}$1 integrin (Aota et al. 1994). (omitted)

  • PDF

Analysis of Toxicity in Escherichia coli from the Expression of Human Purinergic Receptor $P2X_4$ (인간 퓨린수용체 $P2X_4$를 발현시킬 때 나타나는 대장균 독성의 원인분석)

  • Yu, Yon-Joo;Jung, Yun-A;Lim, Dong-Bin
    • Korean Journal of Microbiology
    • /
    • v.47 no.1
    • /
    • pp.7-13
    • /
    • 2011
  • In general, expression of membrane protein in Escherichia coli is very toxic to the host organism, but the mechanism for the toxicity is not clear yet. Expression of human purinergic receptor $P2X_4$ was found to be extremely toxic to the host E. coli. We examined this toxicity by isolation and analysis of less toxic mutant proteins. We could isolate 30 less toxic mutants of $P2X_4$ after hydroxylamine mutagenesis. Western blot showed that all of them produced proteins smaller than the wild type $P2X_4$. DNA sequencing of two largest mutant proteins showed that they were lost its second transmembrane domain. Localization analysis of these mutant proteins showed that they are not in cytoplasmic membrane, but in inclusion bodies. These data showed that inactive truncated $P2X_4$ is not toxic to E. coli and membrane integration and functionality of $P2X_4$ may be needed to show host toxicity.

EP2 Induces p38 Phosphorylation via the Activation of Src in HEK 293 Cells

  • Chun, Kyung-Soo;Shim, Minsub
    • Biomolecules & Therapeutics
    • /
    • v.23 no.6
    • /
    • pp.539-548
    • /
    • 2015
  • Prostaglandin $E_2$ ($PGE_2$), a major product of cyclooxygenase, binds to four different prostaglandin $E_2$ receptors (EP1, EP2, EP3, and EP4) which are G-protein coupled transmembrane receptors (GPCRs). Although GPCRs including EP receptors have been shown to be associated with their specific G proteins, recent evidences suggest that GPCRs can regulate MAPK signaling via non-G protein coupled pathways including Src. EP2 is differentially expressed in various tissues and the expression of EP2 is induced by extracellular stimuli. We hypothesized that an increased level of EP2 expression may affect MAPK signaling. The overexpression of EP2 in HEK 293 cells resulted in significant increase in intracellular cAMP levels response to treatment with butaprost, a specific EP2 agonist, while overexpression of EP2 alone did not increase intracellular cAMP levels. However, EP2 overexpression in the absence of $PGE_2$ induced an increase in the level of p38 phosphorylation as well as the kinase activity of p38, suggesting that up-regulation of EP2 may promote p38 activation via non-G protein coupled pathway. Inhibition of Src completely blocked EP2-induced p38 phosphorylation and overexpression of Src increased the level of p38 phosphorylation, indicating that Src is upstream kinase for EP2-induced p38 phosphorylation. EP2 overexpression also increased the Src activity and EP2 protein was co-immunoprecipitated with Src. Furthermore, sequential co-immunoprecipitation studies showed that EP2, Src, and ${\beta}$-arrestin can form a complex. Our study found a novel pathway in which EP2 is associated with Src, regulating p38 pathway.

Separation and Purification of Lysozyme from Chicken Eggwhite Through Ultrafiltration (한외여과를 통한 난백 중 라이소자임의 분리정제)

  • Koo Ja-Kyung;Son Dongho;Jun Hoejin;Lee Yunhee;Cho Namjun;Jang Dong Il
    • Membrane Journal
    • /
    • v.15 no.2
    • /
    • pp.121-131
    • /
    • 2005
  • Separation and purification of lysozyme from chicken egg white was studied using ultrafiltration. We have obtained experimental data through the cellulose membranes with the molecular weight cut off (MWCO) of 10 kDa, 30 kDa and 100 kDa in a stirred ultrafiltration device. Certain amounts of egg white were dissolved into 20 mM phosphate buffers of pH 6, 7 and 8 to make protein solutions of $1\%,\;2\%,\;3\%\;and\;10\%$ concentration. Permeation flux increased with increasing MWCO of the membrane. Permeation flux increased with increasing transmembrane pressure (TMP) and decreasing the protein concentration. As the MWCO of membrane decreased, the selectivity increased. The selectivity increased with increasing TMP and protein concentration of the solution.

Expression of Smoothened Protein in Colon Cancer and its Prognostic Value for Postoperative Liver Metastasis

  • Ding, Yin-Lu;Wang, Qi-San;Zhao, Wei-Min;Xiang, Lei
    • Asian Pacific Journal of Cancer Prevention
    • /
    • v.13 no.8
    • /
    • pp.4001-4005
    • /
    • 2012
  • Backgrouds: The hedgehog (Hh) signaling pathway is composed of patched (PTCH) and smoothened (SMO), two transmembrane proteins, and downstream glioma-associated oncogene homolog (Gli) transcription factors. Hh signaling plays a pathological role in the occurrence and development of various cancers. Methods: To investigate the expression of SMO protein in colon cancer and its association with clinicopathological parameters and postoperative liver metastasis, immunohistochemistry was performed with paraffin-embedded specimens of 96 cases. Relationships between SMO protein expression and clinicopathological parameters, postoperative liver metastasis were analyzed. Results: IHC examination showed that SMO protein expression was significantly increased in colon cancer tissues compared to normal colon tissues (P = 0.042), positively related to lymph node metastases (P = 0.018) and higher T stages (P = 0.026). Postoperative live metastasis-free survival was significantly longer in the low SMO expression group than in those with high SMO expression ($48.7{\pm}8.02$ months vs $28.0{\pm}6.86$ months, P=0.036). Multivariate analysis showed SMO expression level to be an independent prognostic factor for postoperative live metastasis-free survival (95% confidence interval [CI] =1.46-2.82, P = 0.008). Conclusions: Our results suggest that in patients with colon cancer, the SMO expression level is an independent biomarker for postoperative liver metastasis, and SMO might play an important role in colon cancer progression.

Agronomic characteristics of stay-green mutant derived from an early-maturing rice variety 'Pyeongwon'

  • Won, Yong-Jae;Ji, Hyeon-So;Ahn, Eok-Keun;Lee, Jeong-Heui;Jung, Kuk-Hyun;Lee, Sang-Bok;Hong, Ha-Cheol;Hyun, Ung-Jo;Ha, Woon-Goo;Kim, Myeong-Ki;Kim, Byeong-Ju
    • Proceedings of the Korean Society of Crop Science Conference
    • /
    • 2017.06a
    • /
    • pp.72-72
    • /
    • 2017
  • We found a new stay-green mutant from 'Pyeongwon' which is an early-maturing rice variety in Korea. The mutant showed green leaves after grain ripening period and it maintained higher SPAD value than wild type rice plant and original variety 'Pyeongwon'. The stay-green trait in rice, three genes have been identified up to date. The non-yellow coloring1 (NYC1) gene encodes a chloroplast-localized short-chain dehydrogenase/reductase (SDR) with three transmembrane domains. The non-yellow coloring3 (NYC3) gene encodes a plastid-localizing alpha/beta hydrolase-fold family protein with an esterase/lipase motif. The Sgr gene encodes a novel chloroplast protein and regulates the destabilization of the light-harvesting chlorophyll binding protein (LHCP) complexes of the thylakoid membranes, which is a prerequisite event for the degradation of chlorophylls and LHCPs during senescence. After sequencing the PCR products, we found a single nucleotide variation($A{\rightarrow}T$) in the NYC1 gene, which changes the amino acid lysine to methionine. The NYC1 gene encodes a short-chain dehydrogenase/reductase(SDR) protein. And we confirmed the co-segregation between SNP and stay-green trait from genotyping the progenies of the mutant.

  • PDF