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https://www.readbyqxmd.com/read/29340786/in-silico-identification-and-experimental-validation-of-amino-acid-motifs-required-for-the-rho-of-plants-gtpase-mediated-activation-of-receptor-like-cytoplasmic-kinases
#1
Dézi Bianka Lajkó, Ildikó Valkai, Mónika Domoki, Dalma Ménesi, Györgyi Ferenc, Ferhan Ayaydin, Attila Fehér
Several amino acid motifs required for Rop-dependent activity were found to form a common surface on RLCKVI_A kinases. This indicates a unique mechanism for Rho-type GTPase-mediated kinase activation in plants. Rho-of-plants (Rop) G-proteins are implicated in the regulation of various cellular processes, including cell growth, cell polarity, hormonal and pathogen responses. Our knowledge about the signalling pathways downstream of Rops is continuously increasing. However, there are still substantial gaps in this knowledge...
January 16, 2018: Plant Cell Reports
https://www.readbyqxmd.com/read/29337666/tuning-of-in-vivo-cognate-b-t-cell-interactions-by-intersectin-2-is-required-for-effective-anti-viral-b-cell-immunity
#2
Marianne Burbage, Francesca Gasparrini, Shweta Aggarwal, Mauro Gaya, Johan Arnold, Usha Nair, Michael Way, Andreas Bruckbauer, Facundo D Batista
Wiskott-Aldrich syndrome (WAS) is an immune pathology associated with mutations in WAS protein (WASp) or in WASp interacting protein (WIP). Together with the small GTPase Cdc42 and other effectors, these proteins participate in the remodelling of the actin network downstream of BCR engagement. Here we show that mice lacking the adaptor protein ITSN2, a G-nucleotide exchange factor (GEF) for Cdc42 that also interacts with WASp and WIP, exhibited increased mortality during primary infection, incomplete protection after Flu vaccination, reduced germinal centre formation and impaired antibody responses to vaccination...
January 16, 2018: ELife
https://www.readbyqxmd.com/read/29335451/a-hot-spot-mutation-in-cdc42-p-tyr64cys-and-novel-phenotypes-in-the-third-patient-with-takenouchi-kosaki-syndrome
#3
Midori Motokawa, Satoshi Watanabe, Akiko Nakatomi, Tatsuro Kondoh, Tadashi Matsumoto, Kanako Morifuji, Hirotake Sawada, Toyoki Nishimura, Hiroyuki Nunoi, Koh-Ichiro Yoshiura, Hiroyuki Moriuchi, Sumito Dateki
Takenouchi-Kosaki syndrome (TKS) is a congenital malformation syndrome characterized by severe developmental delay, macrothrombocytopenia, camptodactyly, sensorineural hearing loss, and dysmorphic facial features. Recently, a heterozygous de novo mutation (p.Tyr64Cys) in the CDC42 gene, which encodes a key small GTP-binding protein of the Rho-subfamily, was identified in two unrelated patients with TKS. We herein report a third patient with TKS who had the same heterozygous CDC42 mutation. The phenotype of the patient was very similar to those of the two previously reported patients with TKS; however, she also demonstrated novel clinical manifestations, such as congenital hypothyroidism and immunological disturbance...
January 15, 2018: Journal of Human Genetics
https://www.readbyqxmd.com/read/29331044/journey-of-oocyte-from-metaphase-i-to-metaphase-ii-stage-in-mammals
#4
Alka Sharma, Meenakshi Tiwari, Anumegha Gupta, Ashutosh N Pandey, Pramod K Yadav, Shail K Chaube
In mammals, journey from metaphase-I (M-I) to metaphase-II (M-II) is important since oocyte extrude first polar body (PB-I) and gets converted into haploid gamete. The molecular and cellular changes associated with meiotic cell cycle progression from M-I to M-II stage and extrusion of PB-I remain ill understood. Several factors drive oocyte meiosis from M-I to M-II stage. The mitogen-activated protein kinase3/1 (MAPK3/1), signal molecules and Rho family GTPases act through various pathways to drive cell cycle progression from M-I to M-II stage...
January 13, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29330094/p21-activated-kinase-signaling-in-cancer
#5
REVIEW
Chetan K Rane, Audrey Minden
The p21 Activated Kinases (PAKs) are a family of serine threonine kinases, that consist of 6 members, PAKs 1-6, which are positioned at an intersection of multiple signaling pathways implicated in oncogenesis. The PAKs were originally identified as protein kinases that function downstream of the Ras related Rho GTPases Cdc42 and Rac. PAK1 and PAK4, which belong to Group I and Group II PAKs, respectively, are most often associated with tumorigenesis. On account of their well characterized roles in cancer, several small molecule inhibitors are being developed to inhibit the PAKs, and there is interest in investigating their efficacy as either first line or adjuvant treatments for cancer...
January 9, 2018: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/29330091/cdc42ep4-a-perisynaptic-scaffold-protein-in-bergmann-glia-is-required-for-glutamatergic-tripartite-synapse-configuration
#6
Natsumi Ageta-Ishihara, Kohtarou Konno, Maya Yamazaki, Manabu Abe, Kenji Sakimura, Masahiko Watanabe, Makoto Kinoshita
Configuration of tripartite synapses, comprising the pre-, post-, and peri-synaptic components (axon terminal or bouton, dendritic spine, and astroglial terminal process), is a critical determinant of neurotransmitter kinetics and hence synaptic transmission. However, little is known about molecular basis for the regulation of tripartite synapse morphology. Previous studies showed that CDC42EP4, an effector protein of a cell morphogenesis regulator CDC42, is expressed exclusively in Bergmann glia in the cerebellar cortex, that it forms tight complex with the septin heterooligomer, and that it interacts indirectly with the glutamate transporter GLAST and MYH10/nonmuscle myosin ΙΙB...
January 9, 2018: Neurochemistry International
https://www.readbyqxmd.com/read/29320953/spaceflight-activates-protein-kinase-c-alpha-signaling-and-modifies-the-developmental-stage-of-human-neonatal-cardiovascular-progenitor-cells
#7
Jonathan Baio, Aida F Martinez, Leonard L Bailey, Nahidh Hasaniya, Michael Pecaut, Mary Kearns-Jonker
Spaceflight impacts cardiovascular function in astronauts; however, its impact on cardiac development and the stem cells that form the basis for cardiac repair is unknown. Accordingly, further research is needed to uncover the potential relevance of such changes to human health. Using simulated microgravity (SMG) generated via two-dimensional clinorotation and culture aboard the International Space Station (ISS), we assessed the effects of mechanical unloading on human neonatal cardiovascular progenitor cell (CPC) developmental properties and signaling...
January 10, 2018: Stem Cells and Development
https://www.readbyqxmd.com/read/29314205/cdc42-is-essential-for-both-articular-cartilage-degeneration-and-subchondral-bone-deterioration-in-experimental-osteoarthritis
#8
Xinhua Hu, Xing Ji, Mengting Yang, Shihao Fan, Jirong Wang, Meiping Lu, Wei Shi, Liu Mei, Chengyun Xu, Xueying Fan, Musaddique Hussain, Jingyu Du, Junsong Wu, Ximei Wu
Cdc42, a member of Rho family small GTPases, is critical for cartilage development. We investigated the roles of Cdc42 in osteoarthritis and explored the potential mechanism underlying Cdc42-mediated articular cartilage degeneration and subchondral bone deterioration. Cdc42 is highly expressed in both articular cartilage and subchondral bone in a mouse osteoarthritis model with surgical destabilisation of the medial meniscus (DMM) in the knee joints. Specifically, genetic disruption of Cdc42, knockdown of Cdc42 expression, or inhibition of Cdc42 activity robustly attenuates the DMM-induced destruction, hypertrophy, high expression of matrix metallopeptidase-13 and collagen X, and activation of Stat3 in articular cartilages...
January 3, 2018: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/29307615/protein-phosphatase-1b-dephosphorylates-rho-guanine-nucleotide-dissociation-inhibitor-1-and-suppresses-cancer-cell-migration-and-invasion
#9
Hee Jun Cho, Jong-Tae Kim, Seon-Jin Lee, Yo Sep Hwang, Sang Yoon Park, Bo-Yeon Kim, Jiyun Yoo, Kwan Soo Hong, Jeong-Ki Min, Chul-Ho Lee, Jong-Seok Lim, Suk Ran Yoon, Inpyo Choi, Yong-Kyung Choe, Hee Gu Lee
Rho GTPases control a wide range of cellular processes, and their deregulation is associated with promotion of an aggressive and metastatic tumor phenotype in human cancers. Rho guanine nucleotide dissociation inhibitor 1 (RhoGDI1) plays a key role in regulating the activity of Rho GTPases. However, the underlying mechanisms are still unclear. In this study, we show that protein phosphatase 1B (PPM1B) interacts with RhoGDI1 and functions as its phosphatase. Ectopic expression of PPM1B results in dephosphorylation of RhoGDI1 and, thereby, abates the activation of RhoA, Rac1 and CDC42 by epidermal growth factor (EGF)...
January 4, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29297928/p21-activated-kinase-2-is-essential-in-maintenance-of-peripheral-foxp3-regulatory-t-cells
#10
Jinyong Choi, David Randall Pease, Siqi Chen, Bin Zhang, Hyewon Phee
The p21-activated kinase 2 (Pak2), an effector molecule of the Rho family GTPases Rac and Cdc42, regulates diverse functions of T cells. Previously, we showed that Pak2 is required for development and maturation of T cells in the thymus, including thymus-derived regulatory T cells (tTregs). However, whether Pak2 is required for functions of various subsets of peripheral T cells, such as naïve CD4 and helper T cell subsets including Foxp3+ regulatory T cells (Foxp3+Tregs), is unknown. To determine the role of Pak2 in CD4 T cells in the periphery, we generated inducible Pak2 knockout (KO) mice, in which Pak2 was deleted in CD4 T cells acutely by administration of tamoxifen...
January 3, 2018: Immunology
https://www.readbyqxmd.com/read/29296000/non-canonical-wnt-signaling-regulates-neural-stem-cell-quiescence-during-homeostasis-and-after-demyelination
#11
Manideep Chavali, Michael Klingener, Alexandros G Kokkosis, Yury Garkun, Sylwia Felong, Arianna Maffei, Adan Aguirre
Adult neural stem cells (NSCs) reside in a specialized microenvironment, the subventricular zone (SVZ), which provides them with unique signaling cues to control their basic properties and prevent their exhaustion. While the signaling mechanisms that regulate NSC lineage progression are well characterized, the molecular mechanisms that trigger the activation of quiescent NSCs during homeostasis and tissue repair are still unclear. Here, we uncovered that the NSC quiescent state is maintained by Rho-GTPase Cdc42, a downstream target of non-canonical Wnt signaling...
January 2, 2018: Nature Communications
https://www.readbyqxmd.com/read/29295957/the-depalmitoylase-apt1-directs-the-asymmetric-partitioning-of-notch-and-wnt-signaling-during-cell-division
#12
Ewa Stypulkowski, Irfan A Asangani, Eric S Witze
Asymmetric cell division results in two distinctly fated daughter cells. A molecular hallmark of asymmetric division is the unequal partitioning of cell fate determinants. We have previously established that growth factor signaling promotes protein depalmitoylation to foster polarized protein localization, which, in turn, drives migration and metastasis. We report protein palmitoylation as a key mechanism for the asymmetric partitioning of the cell fate determinants Numb and β-catenin through the activity of the depalmitoylating enzyme APT1...
January 2, 2018: Science Signaling
https://www.readbyqxmd.com/read/29295922/cdc42-binds-pak4-via-an-extended-gtpase-effector-interface
#13
Byung Hak Ha, Titus J Boggon
The p21-activated kinase (PAK) group of serine/threonine kinases are downstream effectors of RHO GTPases and play important roles in regulation of the actin cytoskeleton, cell growth, survival, polarity, and development. Here we probe the interaction of the type II PAK, PAK4, with RHO GTPases. Using solution scattering we find that the full-length PAK4 heterodimer with CDC42 adopts primarily a compact organization. X-ray crystallography reveals the molecular nature of the interaction between PAK4 and CDC42 and shows that in addition to the canonical PAK4 CDC42/RAC interactive binding (CRIB) domain binding to CDC42 there are unexpected contacts involving the PAK4 kinase C-lobe, CDC42, and the PAK4 polybasic region...
January 2, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29288926/efhd2-swiprosin-1-regulates-lps-induced-macrophage-recruitment-via-enhancing-actin-polymerization-and-cell-migration
#14
Ye Tu, Lichao Zhang, Lingchang Tong, Yue Wang, Su Zhang, Rongmei Wang, Ling Li, Zhibin Wang
Macrophage motility is vital in innate immunity, which contributes strategically to the defensive inflammation process. During bacterial infection, lipopolysaccharide (LPS) potently activates the migration of macrophages via the NF-κB/iNOS/c-Src signaling pathway. However, the downstream region of c-Src that participates in macrophage migration is unclear. EFhd2, a novel actin bundling protein, was evaluated for its role in LPS-stimulated macrophage migration in this study. We found that LPS stimulated the up-regulation, tyrosine phosphorylation and membrane translocation of EFhd2 in macrophages...
December 27, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/29285225/the-protective-value-of-mir-204-5p-for-prognosis-and-its-potential-gene-network-in-various-malignancies-a-comprehensive-exploration-based-on-rna-seq-high-throughput-data-and-bioinformatics
#15
Zhi-Hua Ye, Dong-Yue Wen, Xiao-Yong Cai, Liang Liang, Pei-Rong Wu, Hui Qin, Hong Yang, Yun He, Gang Chen
Purpose: The prognostic role of miR-204-5p (previous ID: miR-204) is varied and inconclusive in diverse types of malignant neoplasm. Therefore, the purposes of the study comprehensively explore the overall prognostic role of miR-204-5p based on high-throughput microRNA sequencing data, and to investigate the potential role of miR-204-5p via bioinformatics approaches. Materials and Methods: The data of microRNA sequencing and survival were downloaded from The Cancer Genome Atlas (TCGA), and the prognostic value of miR-204-5p was analyzed by using Kaplan-Meier and univariate cox regressions...
December 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/29285198/total-alkaloids-of-corydalis-saxicola-bunting-inhibits-migration-of-a549-cells-by-suppressing-cdc42-or-vav1
#16
Mimi Li, Jiying Wang, Biwen Mo, Jinrong Zeng, Dong Yao, Feng Chen, Ming Jiang, Lizong Rao, Yinjun Du
Cell division cycle 42 (Cdc42) is a critical regulator, which functions in cancer metastasis. Numerous previous studies have demonstrated that vav guanine nucleotide exchange factor 1 (Vav1) is ectopically expressed in numerous types of human malignancies and have suggested that Vav1 may efficiently promote the formation of invadopodia and matrix degradation by regulating the activation of Cdc42. Total alkaloids of Corydalis saxicola bunting (TAOCSB), a type of alkaloid compound extracted from the root of C...
January 2018: Oncology Letters
https://www.readbyqxmd.com/read/29284478/phoyunnanin-e-inhibits-migration-of-non-small-cell-lung-cancer-cells-via-suppression-of-epithelial-to-mesenchymal-transition-and-integrin-%C3%AE-v-and-integrin-%C3%AE-3
#17
Nareerat Petpiroon, Boonchoo Sritularak, Pithi Chanvorachote
BACKGROUND: The conversion of the epithelial phenotype of cancer cells into cells with a mesenchymal phenotype-so-called epithelial-mesenchymal transition (EMT)-has been shown to enhance the capacity of the cells to disseminate throughout the body. EMT is therefore becoming a potential target for anti-cancer drug discovery. Here, we showed that phoyunnanin E, a compound isolated from Dendrobium venustum, possesses anti-migration activity and addressed its mechanism of action. METHODS: The cytotoxic and proliferative effects of phoyunnanin E on human non-small cell lung cancer-derived H460, H292, and A549 cells and human keratinocyte HaCaT cells were investigated by MTT assay...
December 29, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/29279389/rsk2-drives-cell-motility-by-serine-phosphorylation-of-larg-and-activation-of-rho-gtpases
#18
Geng-Xian Shi, Won Seok Yang, Ling Jin, Michelle L Matter, Joe W Ramos
Directed migration is essential for cell motility in many processes, including development and cancer cell invasion. RSKs (p90 ribosomal S6 kinases) have emerged as central regulators of cell migration; however, the mechanisms mediating RSK-dependent motility remain incompletely understood. We have identified a unique signaling mechanism by which RSK2 promotes cell motility through leukemia-associated RhoGEF (LARG)-dependent Rho GTPase activation. RSK2 directly interacts with LARG and nucleotide-bound Rho isoforms, but not Rac1 or Cdc42...
December 26, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29276218/signal-diversity-of-receptor-for-advanced-glycation-end-products
#19
REVIEW
Masakiyo Sakaguchi, Rie Kinoshita, Endy Widya Putranto, I Made Winarsa Ruma, I Wayan Sumardika, Chen Youyi, Naoko Tomonobu, Ken-Ichi Yamamoto, Hitoshi Murata
The receptor for advanced glycation end products (RAGE) is involved in inflammatory pathogenesis. It functions as a receptor to multiple ligands such as AGEs, HMGB1 and S100 proteins, activating multiple intracellular signaling pathways with each ligand binding. The molecular events by which ligand-activated RAGE controls diverse signaling are not well understood, but some progress was made recently. Accumulating evidence revealed that RAGE has multiple binding partners within the cytoplasm and on the plasma membrane...
December 2017: Acta Medica Okayama
https://www.readbyqxmd.com/read/29251334/niclosamide-acts-as-a-new-inhibitor-of-vasculogenic-mimicry-in-oral-cancer-through-upregulation-of-mir-124-and-downregulation-of-stat3
#20
Xiaoxu Li, Zhicheng Yang, Zewen Han, Yanhui Wen, Zeyun Ma, Yixiang Wang
Tumors require nutrients and oxygen for growth and metastasis. Vasculogenic mimicry (VM) has been found as a new manner of blood supply, which is characterized as the formation of tumor cell-lined vessels instead of endothelial vessels. This is why angiogenesis agents targeted to endothelial cells show a limited efficacy. Up to this point, there is no effective drug reported for inhibiting VM formation. Niclosamide is an oral anti-helminthic drug used to treat human tapeworms. Recent studies have indicated that niclosamide has broad applications for cancer and other diseases...
February 2018: Oncology Reports
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