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https://www.readbyqxmd.com/read/28407694/molecular-mechanisms-of-activating-c-met-in-kshv-primary-effusion-lymphoma
#1
Bao Quoc Lam, Lu Dai, Li Li, Jing Qiao, Zhen Lin, Zhiqiang Qin
The oncogenic Kaposi's sarcoma-associated herpesvirus (KSHV) is a principal causative agent of primary effusion lymphoma (PEL), which is mostly seen in immunosuppressed patients. PEL is a rapidly progressing malignancy with a median survival time of approximately 6 months even under the conventional chemotherapy. We recently report that the hepatocyte growth factor (HGF)/c-MET pathway is highly activated in PEL cells and represents a promising therapeutic target (Blood. 2015;126(26):2821-31). However, the underlying mechanisms of c-MET activation within PEL cells remain largely unknown...
March 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28281763/-15-n-h-related-conformational-entropy-changes-entailed-by-plexin-b1-rbd-dimerization-combined-molecular-dynamics-nmr-relaxation-approach
#2
Mirco Zerbetto, Eva Meirovitch
We report on a new method for determining function-related conformational entropy changes in proteins. Plexin-B1 RBD dimerization serves as example, and internally mobile N-H bonds serve as probes. Sk (entropy in units of kBT) is given by -∫(PeqlnPeq)dΩ, where Peq = exp(-u) is the probability density for probe orientation, and u the local potential. Previous slowly relaxing local structure (SRLS) analyses of (15)N-H relaxation in proteins determined linear combinations of D00(2)(Ω) and (D02(2)(Ω) + D0-2(2)(Ω)) (D0K(L)(Ω) represents a Wigner rotation matrix element in uniaxial local medium) as "best-fit" form of u...
March 30, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28280798/endometrial-expression-of-%C3%AE-3-integrin-calcitonin-and-plexin-b1-in-the-window-of-implantation-in-women-with-unexplained-infertility
#3
Mehran Dorostghoal, Hamid-O-Allah Ghaffari, Nahid Shahbazian, Maryam Mirani
BACKGROUND: Endometrial receptivity plays a key role in the establishment of successful implantation and its impairment may contribute to subfertility and limit the assisted reproduction techniques (ART) success. OBJECTIVE: The aim of present study was to investigate endometrial receptivity in terms of β3 integrin, calcitonin and plexin-B1 expression in women with unexplained infertility. MATERIALS AND METHODS: We evaluated expression of β3 integrin, calcitonin and plexin-B1 through mRNA level measurement with real-time RT-PCR, in the endometrium of 16 infertile women with unexplained infertility and 10 fertile women...
January 2017: International Journal of Reproductive Biomedicine (Yazd, Iran)
https://www.readbyqxmd.com/read/28103666/molecular-dynamics-simulations-reveal-isoform-specific-contact-dynamics-between-the-plexin-rho-gtpase-binding-domain-rbd-and-small-rho-gtpases-rac1-and-rnd1
#4
Liqun Zhang, Matthias Buck
The Plexin family of transmembrane receptors are unique in that their intracellular region interacts directly with small GTPases of the Rho family. The Rho GTPase binding domain of plexin (RBD)-which is responsible for these interactions-can bind with Rac1 as well as Rnd1 GTPases. GTPase complexes have been crystallized with the RBDs of plexinA1, -A2, and -B1. The protein association is thought to elicit different functional responses in a GTPase and plexin isoform specific manner, but the origin of this is unknown...
February 8, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28038319/recruitment-of-tiam1-to-semaphorin-4d-activates-rac-and-enhances-proliferation-invasion-and-metastasis-in-oral-squamous-cell-carcinoma
#5
Hua Zhou, Maricel G Kann, Emily K Mallory, Ying-Hua Yang, Amr Bugshan, Nada O Binmadi, John R Basile
The semaphorins and the plexins are a family of large, cysteine-rich proteins originally identified as regulators of axon growth and lymphocyte activation that are now known to provide motility and positional information for a number of cell and tissue types. For example, our group and others have shown that some malignancies over express Semaphorin 4D (S4D), which acts through its receptor Plexin-B1 (PB1) on endothelial cells to attract blood vessels from the surrounding stroma for the purpose of supporting tumor growth...
February 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28027822/semaphorin-4d-enhances-angiogenic-potential-and-suppresses-osteo-odontogenic-differentiation-of-human-dental-pulp-stem-cells
#6
Ting Zou, Waruna Lakmal Dissanayaka, Shan Jiang, Shuai Wang, Boon Chin Heng, Xiaojing Huang, Chengfei Zhang
INTRODUCTION: To investigate the roles of semaphorin 4D (Sema4D)/plexin-B1 signaling on the angiogenic potential and osteo-/odontogenic differentiation of human dental pulp stem cells (DPSCs) and to uncover the corresponding molecular mechanisms. METHODS: DPSCs were treated with Sema4D (10 μg/mL) for different time durations. Osteo-/odontogenic differentiation was assessed by quantifying alkaline phosphatase activity, mineralized nodule formation, and osteo-/odontogenic gene (ALP, Col1A1, BSP, RUNX2, and DSPP) and protein (Col1A1 and DSPP) expression...
December 24, 2016: Journal of Endodontics
https://www.readbyqxmd.com/read/28007914/a-reverse-signaling-pathway-downstream-of-sema4a-controls-cell-migration-via-scrib
#7
Tianliang Sun, Lida Yang, Harmandeep Kaur, Jenny Pestel, Mario Looso, Hendrik Nolte, Cornelius Krasel, Daniel Heil, Ramesh K Krishnan, Marie-Josée Santoni, Jean-Paul Borg, Moritz Bünemann, Stefan Offermanns, Jakub M Swiercz, Thomas Worzfeld
Semaphorins comprise a large family of ligands that regulate key cellular functions through their receptors, plexins. In this study, we show that the transmembrane semaphorin 4A (Sema4A) can also function as a receptor, rather than a ligand, and transduce signals triggered by the binding of Plexin-B1 through reverse signaling. Functionally, reverse Sema4A signaling regulates the migration of various cancer cells as well as dendritic cells. By combining mass spectrometry analysis with small interfering RNA screening, we identify the polarity protein Scrib as a downstream effector of Sema4A...
January 2, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28004109/identification-of-tmprss2-erg-mechanisms-in-prostate-cancer-invasiveness-involvement-of-mmp-9-and-plexin-b1
#8
Bide Liu, Xiao Gu, Tianbao Huang, Yang Luan, Xuefei Ding
The relationship of TMPRSS2-ERG fusion gene with matrix metalloproteinase-9 (MMP-9) and PLXNB1 (plexin B1) in regulation of prostate cancer (PCa) aggressiveness was investigated. Fluorescence in situ hybridization (FISH) assays, qRT-PCR and western blot analysis were employed to detect the expression of TMPRSS2-ERG fusion gene, ERG, MMP-9 and PLXNB1 of 135 human tissues, which included 55 metastatic PCa cases, 50 localized PCa cases and 30 BPH cases. Then using siRNA (anti-ERG, MMP-9 and PLXNB1, respectively) downregulation of the target gene of VCaP and PC-3 cells, MTT and Transwell were performed...
January 2017: Oncology Reports
https://www.readbyqxmd.com/read/27984026/allosteric-inhibition-of-a-semaphorin-4d-receptor-plexin-b1-by-a-high-affinity-macrocyclic-peptide
#9
Yukiko Matsunaga, Nasir K Bashiruddin, Yu Kitago, Junichi Takagi, Hiroaki Suga
Semaphorin axonal guidance factors are multifunctional proteins that play important roles in immune response, cancer cell proliferation, and organogenesis, making semaphorins and their signaling receptor plexins important drug targets for various diseases. However, the large and flat binding surface of the semaphorin-plexin interaction interface is difficult to target by traditional small-molecule drugs. Here, we report the discovery of a high-affinity plexin B1 (PlxnB1)-binding macrocyclic peptide, PB1m6 (KD = 3...
November 17, 2016: Cell Chemical Biology
https://www.readbyqxmd.com/read/27787869/characterization-of-the-effects-of-semaphorin-4d-signaling-on-angiogenesis
#10
Hua Zhou, Ying-Hua Yang, John R Basile
The semaphorins and plexins comprise a family of cysteine-rich cell surface and secreted proteins originally shown to control nerve growth and the immune response, but that have recently been implicated in a wide variety of developmental and pathological processes that are influenced by cell adhesion and migration. Along those lines, our group and others have found that Semaphorin 4D (SEMA4D) plays an important role in angiogenesis by promoting chemotaxis of endothelial cells, which express its receptor, Plexin-B1...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27787844/characterizing-plexin-gtpase-interactions-using-gel-filtration-surface-plasmon-resonance-spectrometry-and-isothermal-titration-calorimetry
#11
Jeannine Muller-Greven, SoonJeung Kim, Prasanta K Hota, Yufeng Tong, Susmita Borthakur, Matthias Buck
Plexins are unique, as they are the first example of a transmembrane receptor that interacts directly with small GTPases, a family of proteins that are essential for cell motility and proliferation/survival. We and other laboratories have determined the structure of the Rho GTPase-binding domain (RBD) of several plexins and also of the entire intracellular region of plexin-B1. Structures of plexin complexes with Rho GTPases, Rac1 and Rnd1, and a structure with a Ras GTPase, Rap1b, have also been solved. The relationship between plexin-Rho and plexin-Ras interactions is still unclear and in vitro biophysical experiments that characterize the protein interactions of purified components play an important role in advancing our understanding of the molecular mechanisms that underlie the function of plexin...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27218883/the-semaphorin-4d-rhoa-akt-signal-cascade-regulates-enamel-matrix-secretion-in-coordination-with-cell-polarization-during-ameloblast-differentiation
#12
Keishi Otsu, Hiroko Ida-Yonemochi, Naoki Fujiwara, Hidemitsu Harada
During tooth development, oral epithelial cells differentiate into ameloblasts in order to form the most mineralized tissue in the vertebrate body: enamel. During this process, ameloblasts directionally secrete enamel matrix proteins and morphologically change from low columnar cells to polarized tall columnar cells, both of which are essential for the proper formation of enamel. In this study, we elucidated the molecular mechanism that integrates ameloblast function and morphology. Immunohistochemistry revealed that the restricted expression of semaphorin 4D (Sema4D) and RhoA activation status are closely associated with ameloblast differentiation in mouse incisors...
May 24, 2016: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/26944058/plexin-b1-indirectly-affects-glioma-invasiveness-and-angiogenesis-by-regulating-the-rhoa-%C3%AE-v%C3%AE-3-signaling-pathway-and-srpk1
#13
Yingwei Chang, Li Li, Luping Zhang, Xuyan Guo, Zhuoying Feng, Junchen Zhou, Shuai Zhou, Guoying Feng, Fengchan Han, Wenhua Huang, Jun Yang, Fei Huang
Gliomas are one of the most common primary brain tumors in adults. They display aggressive invasiveness, are highly vascular, and have a poor prognosis. Plexin-B1 is involved in numerous cellular processes, especially cellular migration and angiogenesis. However, the role and regulatory mechanisms of Plexin-B1 in gliomas are not understood and were thus investigated in this study. By using multiple and diverse experimental techniques, we investigated cell apoptosis, mitochondrial membrane potential, cell migration and invasion, angiogenesis, PI3K and Akt phosphorylation, and also the levels of SRPK1 and αvβ3 in glioma cells and animal glioma tissues...
August 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/26938937/local-ordering-at-mobile-sites-in-proteins-from-nuclear-magnetic-resonance-relaxation-the-role-of-site-symmetry
#14
Oren Tchaicheeyan, Jack H Freed, Eva Meirovitch
Restricted motions in proteins (e.g., N-H bond dynamics) are studied effectively with NMR. By analogy with restricted motions in liquid crystals (LC), the local ordering has in the past been primarily represented by potentials comprising the L = 2, |K| = 0, 2 spherical harmonics. However, probes dissolved in LCs experience nonpolar ordering, often referred to as alignment, while protein-anchored probes experience polar ordering, often referred to as orientation. In this study we investigate the role of local (site) symmetry in the context of the polarity of the local ordering...
March 24, 2016: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/26910109/semaphorin-4d-promotes-skeletal-metastasis-in-breast-cancer
#15
Ying-Hua Yang, Asma Buhamrah, Abraham Schneider, Yi-Ling Lin, Hua Zhou, Amr Bugshan, John R Basile
Bone density is controlled by interactions between osteoclasts, which resorb bone, and osteoblasts, which deposit it. The semaphorins and their receptors, the plexins, originally shown to function in the immune system and to provide chemotactic cues for axon guidance, are now known to play a role in this process as well. Emerging data have identified Semaphorin 4D (Sema4D) as a product of osteoclasts acting through its receptor Plexin-B1 on osteoblasts to inhibit their function, tipping the balance of bone homeostasis in favor of resorption...
2016: PloS One
https://www.readbyqxmd.com/read/26732941/the-role-of-sema4d-cd100-as-a-therapeutic-target-for-tumor-microenvironments-and-for-autoimmune-neuroimmune-and-bone-diseases
#16
Mingfu Wu, Jing Li, Qinglei Gao, Fei Ye
INTRODUCTION: Semaphorin 4D (Sema4D), also known as CD100, has been implicated in physiologic roles in the immune and nervous systems. However, the interaction of Sema4D with its high affinity receptor, Plexin-B1, reveals a novel role for Sema4D produced by the tumor microenvironment in tumor angiogenesis and metastasis. AREAS COVERED: The ligation of Sema4D/CD100 with CD72 on immune and inflammatory cells is known to stimulate immune responses and regulation. Because CD100 and CD72 are expressed on lung immune and nonimmune cells, as well as on mast cells, the CD100/CD72 interaction plays another important role in allergic airway inflammation and mast cell functions...
July 2016: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/26524400/stimulation-of-vasculogenesis-and-leukopoiesis-of-embryonic-stem-cells-by-extracellular-transfer-rna-and-ribosomal-rna
#17
Fatemeh Sharifpanah, Sepali De Silva, Mohamed M Bekhite, Jorge Hurtado-Oliveros, Klaus T Preissner, Maria Wartenberg, Heinrich Sauer
OBJECTIVE: Cell injury releases nucleic acids supporting inflammation and stem cell activation. Here, the impact of extracellular ribonucleic acid, especially transfer RNA (ex-tRNA), on vasculogenesis and leukopoiesis of mouse embryonic stem (ES) cells was investigated. APPROACH AND RESULTS: ex-tRNA, whole cell RNA and ribosomal RNA (ex-rRNA) but not DNA increased CD31-positive vascular structures in embryoid bodies. Ex-tRNA and ex-rRNA increased numbers of VEGFR2(+), CD31(+) and VE-cadherin(+) vascular cells as well as CD18(+), CD45(+) and CD68(+) cells, indicating leukocyte/macrophage differentiation...
December 2015: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/26489627/role-of-inhibition-of-osteogenesis-function-by-sema4d-plexin-b1-signaling-pathway-in-skeletal-fluorosis-in-vitro
#18
Xiao-li Liu, Jing Song, Ke-jian Liu, Wen-peng Wang, Chang Xu, Yu-zeng Zhang, Yun Liu
Skeletal fluorosis is a chronically metabolic bone disease with extensive hyperostosis osteosclerosis caused by long time exposure to fluoride. Skeletal fluorosis brings about a series of abnormal changes of the extremity, such as joint pain, joint stiffness, bone deformity, etc. Differentiation and maturation of osteoblasts were regulated by osteoclasts via Sema4D/Plexin-B1 signaling pathway. Furthermore, the differentiation and maturation of osteoclasts are conducted by osteoblasts via RANKL/RANK/OPG pathway...
October 2015: Journal of Huazhong University of Science and Technology. Medical Sciences
https://www.readbyqxmd.com/read/26389656/tax-and-semaphorin-4d-released-from-lymphocytes-infected-with-human-lymphotropic-virus-type-1-and-their-effect-on-neurite-growth
#19
Sebastián Quintremil, Carolina Alberti, Matías Rivera, Fernando Medina, Javier Puente, Luis Cartier, Eugenio Ramírez, Yuetsu Tanaka, M Antonieta Valenzuela
Human lymphotropic virus type 1 (HTLV-1) is a retrovirus causing HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), a neurodegenerative central nervous system (CNS) axonopathy. This virus mainly infects CD4(+) T lymphocytes without evidence of neuronal infection. Viral Tax, secreted from infected lymphocytes infiltrated in the CNS, is proposed to alter intracellular pathways related to axonal cytoskeleton dynamics, producing neurological damage. Previous reports showed a higher proteolytic release of soluble Semaphorin 4D (sSEMA-4D) from CD4(+) T cells infected with HTLV-1...
January 2016: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/26303122/expression-of-semaphorin-4a-and-its-potential-role-in-rheumatoid-arthritis
#20
Lin Wang, Guanhua Song, Yabing Zheng, Weiwei Tan, Jihong Pan, Yu Zhao, Xiaotian Chang
INTRODUCTION: Semaphorin 4A (Sema4A) plays critical roles in many physiological and pathological processes including neuronal development, angiogenesis, immune response regulation, autoimmunity, and infectious diseases. The present study aimed to investigate its expression and biological activity in rheumatoid arthritis (RA). METHODS: RNA and protein were isolated from synovial tissues in RA and osteoarthritis (OA) patients. Treatment with recombinant human Sema4A (rhSema4A) or small interfering RNA (siRNA) was applied to examine its effect on the biological activity of synovial fibroblasts of RA (RASFs)...
2015: Arthritis Research & Therapy
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