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https://www.readbyqxmd.com/read/29746010/rho-kinase-rock-collaborates-with-pak-to-regulate-actin-polymerization-and-contraction-in-airway-smooth-muscle
#1
Wenwu Zhang, Bhupal P Bhetwal, Susan J Gunst
KEY POINTS: The mechanisms by which Rho kinase (ROCK) regulates airway smooth muscle contraction were determined in tracheal smooth muscle tissues. ROCK may mediate smooth muscle contraction by inhibiting myosin regulatory light chain (RLC) phosphatase. ROCK can also regulate F-actin dynamics during cell migration, and actin polymerization is critical for airway smooth muscle contraction. Our results show that ROCK does not regulate airway smooth muscle contraction by inhibiting myosin RLC phosphatase or by stimulating myosin RLC phosphorylation...
May 10, 2018: Journal of Physiology
https://www.readbyqxmd.com/read/29554125/git1-regulates-synaptic-structural-plasticity-underlying-learning
#2
Amanda C Martyn, Krisztian Toth, Robert Schmalzigaug, Nathan G Hedrick, Ramona M Rodriguiz, Ryohei Yasuda, William C Wetsel, Richard T Premont
The signaling scaffold protein GIT1 is expressed widely throughout the brain, but its function in vivo remains elusive. Mice lacking GIT1 have been proposed as a model for attention deficit-hyperactivity disorder, due to alterations in basal locomotor activity as well as paradoxical locomotor suppression by the psychostimulant amphetamine. Since we had previously shown that GIT1-knockout mice have normal locomotor activity, here we examined GIT1-deficient mice for ADHD-like behavior in more detail, and find neither hyperactivity nor amphetamine-induced locomotor suppression...
2018: PloS One
https://www.readbyqxmd.com/read/29521005/pgc1%C3%AE-organizes-the-osteoclast-cytoskeleton-by-mitochondrial-biogenesis-and-activation
#3
Yan Zhang, Nidhi Rohatgi, Deborah J Veis, Joel Schilling, Steven L Teitelbaum, Wei Zou
Osteoclasts are mitochondria-rich cells, but the role of these energy-producing organelles in bone resorption is poorly defined. To this end, we conditionally deleted the mitochondria-inducing co-activator, PGC1β, in myeloid lineage cells to generate PGC1βLysM mice. In contrast to previous reports, PGC1β-deficient macrophages differentiate normally into osteoclasts albeit with impaired resorptive function due to cytoskeletal disorganization. Consequently, bone mass of PGC1βLysM mice is double that of wild type...
March 8, 2018: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/29452267/git2-a-keystone-in-ageing-and-age-related-disease
#4
REVIEW
Jaana van Gastel, Jan Boddaert, Areta Jushaj, Richard T Premont, Louis M Luttrell, Jonathan Janssens, Bronwen Martin, Stuart Maudsley
Since its discovery, G protein-coupled receptor kinase-interacting protein 2, GIT2, and its family member, GIT1, have received considerable interest concerning their potential key roles in regulating multiple inter-connected physiological and pathophysiological processes. GIT2 was first identified as a multifunctional protein that is recruited to G protein-coupled receptors (GPCRs) during the process of receptor internalization. Recent findings have demonstrated that perhaps one of the most important effects of GIT2 in physiology concerns its role in controlling multiple aspects of the complex ageing process...
May 2018: Ageing Research Reviews
https://www.readbyqxmd.com/read/29191942/%C3%AE-pix-plays-an-important-role-in-regulation-of-intestinal-epithelial-restitution-by-interacting-with-git1-and-rac1-after-wounding
#5
Navneeta Rathor, Hee Kyoung Chung, Shelley R Wang, Michael Qian, Douglas J Turner, Jian-Ying Wang, Jaladanki N Rao
Early gut mucosal restitution is a process by which intestinal epithelial cells (IECs) migrate over the wounded area, and its defective regulation occurs commonly in various critical pathological conditions. This rapid reepithelialization is mediated by different activating small GTP-binding proteins, but the exact mechanism underlying this process remains largely unknown. Recently, it has been reported that interaction between p21-activated kinase-interacting exchange factor (β-PIX) and G protein-coupled receptor kinase-interacting protein 1 (GIT1) activates small GTPases and plays an important role in the regulation of cell motility...
March 1, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/29150658/differential-regulation-of-synaptic-ap-2-clathrin-vesicle-uncoating-in-synaptic-plasticity
#6
Ermes Candiello, Ratnakar Mishra, Bernhard Schmidt, Olaf Jahn, Peter Schu
AP-1/σ1B-deficiency causes X-linked intellectual disability. AP-1/σ1B -/- mice have impaired synaptic vesicle recycling, fewer synaptic vesicles and enhanced endosome maturation mediated by AP-1/σ1A. Despite defects in synaptic vesicle recycling synapses contain two times more endocytic AP-2 clathrin-coated vesicles. We demonstrate increased formation of two classes of AP-2/clathrin coated vesicles. One which uncoats readily and a second with a stabilised clathrin coat. Coat stabilisation is mediated by three molecular mechanisms: reduced recruitment of Hsc70 and synaptojanin1 and enhanced μ2/AP-2 phosphorylation and activation...
November 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29061650/rac3-regulates-breast-cancer-invasion-and-metastasis-by-controlling-adhesion-and-matrix-degradation
#7
Sara K Donnelly, Ramon Cabrera, Serena P H Mao, John R Christin, Bin Wu, Wenjun Guo, Jose Javier Bravo-Cordero, John S Condeelis, Jeffrey E Segall, Louis Hodgson
The initial step of metastasis is the local invasion of tumor cells into the surrounding tissue. Invadopodia are actin-based protrusions that mediate the matrix degradation necessary for invasion and metastasis of tumor cells. We demonstrate that Rac3 GTPase is critical for integrating the adhesion of invadopodia to the extracellular matrix (ECM) with their ability to degrade the ECM in breast tumor cells. We identify two pathways at invadopodia important for integrin activation and delivery of matrix metalloproteinases: through the upstream recruiter CIB1 as well as the downstream effector GIT1...
December 4, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28981399/the-arf-gap-and-protein-scaffold-cat1-git1-as-a-multifaceted-regulator-of-cancer-progression
#8
Sungsoo M Yoo, Richard A Cerione, Marc A Antonyak
Cool-associated tyrosine phosphorylated protein 1 (Cat1), also referred to as GPCR-kinase interacting protein 1 (Git1), is a ubiquitously expressed, multi-domain protein that is best known for regulating cell shape and migration. Cat1/Git1 functions as a GTPase activating protein (GAP) that inactivates certain members of the ADP-ribosylation factor (Arf) family of small GTPases. It is also a scaffold that brings together several signaling proteins at specific locations within the cell, ensuring their efficient activation...
October 5, 2017: Small GTPases
https://www.readbyqxmd.com/read/28948080/interaction-effects-of-git1-and-drd4-gene-variants-on-continuous-performance-test-variables-in-patients-with-adhd
#9
Hyojin Kim, Johanna Inhyang Kim, Haebin Kim, Jae-Won Kim, Bung-Nyun Kim
INTRODUCTION: The G protein-coupled receptor kinase interacting protein 1 gene (GIT1) has been proposed to be a risk gene for attention deficit hyperactivity disorder (ADHD), and it regulates the endocytosis of G protein-coupled receptors like dopamine receptors. The purpose of this study was to investigate the interaction effects of GIT1 and dopamine receptor D4 (DRD4) gene variants on variables of the continuous performance test (CPT). METHODS: This study recruited 255 ADHD patients and 98 healthy controls (HC) who underwent CPT and genetic analyses...
September 2017: Brain and Behavior
https://www.readbyqxmd.com/read/28942352/myo18a-an-unusual-myosin
#10
REVIEW
Matthew D Buschman, Seth J Field
MYO18A is a divergent member of the myosin family characterized by the presence of an amino-terminal PDZ domain. MYO18A has been found in a few different complexes involved in intracellular transport processes. MYO18A is found in a complex with LURAP1 and MRCK that functions in retrograde treadmilling of actin. It also has been found in a complex with PAK2, βPIX, and GIT1, functioning to transport that protein complex from focal adhesions to the leading edge. Finally, a high proportion of MYO18A is found in complex with GOLPH3 at the trans Golgi, where it functions to promote vesicle budding for Golgi-to-plasma membrane trafficking...
January 2018: Advances in Biological Regulation
https://www.readbyqxmd.com/read/28912643/decreased-glial-gaba-and-tonic-inhibition-in-cerebellum-of-mouse-model-for-attention-deficit-hyperactivity-disorder-adhd
#11
Yoo Sung Kim, Junsung Woo, C Justin Lee, Bo-Eun Yoon
About 5~12% of school-aged children suffer from the Attention-Deficit/Hyperactivity Disorder (ADHD). However, the core mechanism of ADHD remains unclear. G protein-coupled receptor kinase-interacting protein-1 (GIT1) has recently been reported to be associated with ADHD in human and the genetic deletion of GIT1 result in ADHD-like behaviors in mice. Mice lacking GIT1 shows a shift in neuronal excitation/inhibition (E/I) balance. However, the pricise mechanism for E/I imbalance and the role of neuron-glia interaction in GIT1 knockout (KO) mice have not been studied...
August 2017: Experimental Neurobiology
https://www.readbyqxmd.com/read/28759023/mecp2-a-target-of-mir-638-facilitates-gastric-cancer-cell-proliferation-through-activation-of-the-mek1-2-erk1-2-signaling-pathway-by-upregulating-git1
#12
L Y Zhao, D D Tong, M Xue, H L Ma, S Y Liu, J Yang, Y X Liu, B Guo, L Ni, L Y Liu, Y N Qin, L M Wang, X G Zhao, C Huang
Methyl-CpG binding protein 2 (MeCP2) is involved in the carcinogenesis and progression of multiple types of cancer. However, its precise role in gastric cancer (GC) and the relevant molecular mechanism remain unknown. In the present study, we found that miR-638 levels were lower in GC tissues and GC cell lines than in adjacent normal tissues and normal gastric epithelial cell lines, respectively. Low miR-638 levels were associated with poor tumor differentiation, tumor size and lymph node metastasis. MeCP2 expression levels were higher in GC tissues than in adjacent normal tissues...
July 31, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28754105/git1-gene-deletion-delays-chondrocyte-differentiation-and-healing-of-tibial-plateau-fracture-through-suppressing-proliferation-and-apoptosis-of-chondrocyte
#13
Peng Chen, Wan-Li Gu, Ming-Zhi Gong, Jun Wang, Dong-Qing Li
BACKGROUND: Although tibial plateau fracture is an uncommon injury, its regulation is challenging and there are some influencing factors, including the effects of severe bone displacement, depression and cancellous bone cartilage, and inevitable cartilage damage. And GIT1 plays an important role in bone mass and 78 osteoblast cell migration. METHODS: The study used 72 C57/BL6 mice. A tibial plateau fracture model was established by using mice with the same number of GIT1 gene deletions (the experimental group) and their wild-type littermates (the control group)...
July 28, 2017: BMC Musculoskeletal Disorders
https://www.readbyqxmd.com/read/28600779/the-landscape-of-genetic-diseases-in-saudi-arabia-based-on-the-first-1000-diagnostic-panels-and-exomes
#14
Dorota Monies, Mohamed Abouelhoda, Moeenaldeen AlSayed, Zuhair Alhassnan, Maha Alotaibi, Husam Kayyali, Mohammed Al-Owain, Ayaz Shah, Zuhair Rahbeeni, Mohammad A Al-Muhaizea, Hamad I Alzaidan, Edward Cupler, Saeed Bohlega, Eissa Faqeih, Maha Faden, Banan Alyounes, Dyala Jaroudi, Ewa Goljan, Hadeel Elbardisy, Asma Akilan, Renad Albar, Hesham Aldhalaan, Shamshad Gulab, Aziza Chedrawi, Bandar K Al Saud, Wesam Kurdi, Nawal Makhseed, Tahani Alqasim, Heba Y El Khashab, Hamoud Al-Mousa, Amal Alhashem, Imaduddin Kanaan, Talal Algoufi, Khalid Alsaleem, Talal A Basha, Fathiya Al-Murshedi, Sameena Khan, Adila Al-Kindy, Maha Alnemer, Sami Al-Hajjar, Suad Alyamani, Hasan Aldhekri, Ali Al-Mehaidib, Rand Arnaout, Omar Dabbagh, Mohammad Shagrani, Dieter Broering, Maha Tulbah, Amal Alqassmi, Maisoon Almugbel, Mohammed AlQuaiz, Abdulaziz Alsaman, Khalid Al-Thihli, Raashda A Sulaiman, Wajeeh Al-Dekhail, Abeer Alsaegh, Fahad A Bashiri, Alya Qari, Suzan Alhomadi, Hisham Alkuraya, Mohammed Alsebayel, Muddathir H Hamad, Laszlo Szonyi, Faisal Abaalkhail, Sulaiman M Al-Mayouf, Hamad Almojalli, Khalid S Alqadi, Hussien Elsiesy, Taghreed M Shuaib, Mohammed Zain Seidahmed, Ibraheem Abosoudah, Hana Akleh, Abdulaziz AlGhonaium, Turki M Alkharfy, Fuad Al Mutairi, Wafa Eyaid, Abdullah Alshanbary, Farrukh R Sheikh, Fahad I Alsohaibani, Abdullah Alsonbul, Saeed Al Tala, Soher Balkhy, Randa Bassiouni, Ahmed S Alenizi, Maged H Hussein, Saeed Hassan, Mohamed Khalil, Brahim Tabarki, Saad Alshahwan, Amira Oshi, Yasser Sabr, Saad Alsaadoun, Mustafa A Salih, Sarar Mohamed, Habiba Sultana, Abdullah Tamim, Moayad El-Haj, Saif Alshahrani, Dalal K Bubshait, Majid Alfadhel, Tariq Faquih, Mohamed El-Kalioby, Shazia Subhani, Zeeshan Shah, Nabil Moghrabi, Brian F Meyer, Fowzan S Alkuraya
In this study, we report the experience of the only reference clinical next-generation sequencing lab in Saudi Arabia with the first 1000 families who span a wide-range of suspected Mendelian phenotypes. A total of 1019 tests were performed in the period of March 2016-December 2016 comprising 972 solo (index only), 14 duo (parents or affected siblings only), and 33 trio (index and parents). Multigene panels accounted for 672 tests, while whole exome sequencing (WES) represented the remaining 347 tests. Pathogenic or likely pathogenic variants that explain the clinical indications were identified in 34% (27% in panels and 43% in exomes), spanning 279 genes and including 165 novel variants...
August 2017: Human Genetics
https://www.readbyqxmd.com/read/28362242/arf-gaps-a-family-of-proteins-with-disparate-functions-that-converge-on-a-common-structure-the-integrin-adhesion-complex
#15
Teresa Vitali, Sofia Girald-Berlingeri, Paul A Randazzo, Pei-Wen Chen
ADP-ribosylation factors (Arfs) are members of the Ras GTPase superfamily. The function of Arfs is dependent on GTPase-activating proteins (GAPs) and guanine nucleotide exchange factors (GEFs), which allow Arfs to cycle between the GDP-bound and GTP-bound forms. Arf GAPs have been shown to be present in integrin adhesion complexes, which include focal adhesions. Integrin adhesion complexes are composed of integrins, scaffolding proteins and signaling proteins and regulate cell proliferation, survival, differentiation and migration...
March 31, 2017: Small GTPases
https://www.readbyqxmd.com/read/28325781/20-hete-signals-through-g-protein-coupled-receptor-gpr75-gq-to-affect-vascular-function-and-trigger-hypertension
#16
Victor Garcia, Ankit Gilani, Brian Shkolnik, Varunkumar Pandey, Frank Fan Zhang, Rambabu Dakarapu, Shyam K Gandham, N Rami Reddy, Joan P Graves, Artiom Gruzdev, Darryl C Zeldin, Jorge H Capdevila, John R Falck, Michal Laniado Schwartzman
RATIONALE: 20-Hydroxyeicosatetraenoic acid (20-HETE), one of the principle cytochrome P450 eicosanoids, is a potent vasoactive lipid whose vascular effects include stimulation of smooth muscle contractility, migration, and proliferation, as well as endothelial cell dysfunction and inflammation. Increased levels of 20-HETE in experimental animals and in humans are associated with hypertension, stroke, myocardial infarction, and vascular diseases. OBJECTIVE: To date, a receptor/binding site for 20-HETE has been implicated based on the use of specific agonists and antagonists...
May 26, 2017: Circulation Research
https://www.readbyqxmd.com/read/28101188/mir-125a-3p-targetedly-regulates-git1-expression-to-inhibit-osteoblastic-proliferation-and-differentiation
#17
Xiao-Mei Tu, Yang-Lin Gu, Guo-Qin Ren
Osteoblasts are a prerequisite for osteogenesis and bone formation, and play a key role in metabolic balance, growth, development and wound repair. G protein-coupled receptor kinase interacting protein 1 (GIT1) and a series of miRNAs are known to have important effects in the growth and migration of osteoblasts, but little is known about micro RNAs (miRNAs) targeting GIT1. The present study found that miR-125a-3p has matching sites on GIT1. In the osteoblastic differentiation process of human bone marrow-derived mesenchymal stem cells (HMSCs), the expression of miR-125a-3p was suppressed compared with that in non-differentiating (HMSCs) while the expression of GIT1 showed a gradual and significant increase...
December 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28087248/corrigendum-to-git1-betapix-signaling-proteins-and-pak1-kinase-regulate-microtubule-nucleation-biochim-biophys-acta-1863-6pa-2016-1282-1297
#18
Markéta Černohorská, Vadym Sulimenko, Zuzana Hájková, Tetyana Sulimenko, Vladimíra Sládková, Stanislav Vinopal, Eduarda Dráberová, Pavel Dráber
No abstract text is available yet for this article.
April 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27926858/g-protein-coupled-receptor-2-interacting-protein-1-controls-stalk-cell-fate-by-inhibiting-delta-like-4-notch1-signaling
#19
Syamantak Majumder, GuoFu Zhu, Xiangbin Xu, Sharon Senchanthisai, Dongyang Jiang, Hao Liu, Chao Xue, Xiaoqun Wang, Heidi Coia, Zhaoqiang Cui, Elaine M Smolock, Richard T Libby, Bradford C Berk, Jinjiang Pang
The spatiotemporal localization and expression of Dll4 are critical for sprouting angiogenesis. However, the related mechanisms are poorly understood. Here, we show that G-protein-coupled receptor-kinase interacting protein-1 (GIT1) is a robust endogenous inhibitor of Dll4-Notch1 signaling that specifically controls stalk cell fate. GIT1 is highly expressed in stalk cells but not in tip cells. GIT1 deficiency remarkably enhances Dll4 expression and Notch1 signaling, resulting in impaired retinal sprouting angiogenesis, which can be rescued by treatment with the Notch inhibitor or Dll4 neutralizing antibody...
December 6, 2016: Cell Reports
https://www.readbyqxmd.com/read/27922692/mir-195-inhibits-the-proliferation-and-migration-of-chondrocytes-by-targeting-git1
#20
Yang-Lin Gu, Xiao-Xu Rong, Li-Ting Wen, Guo-Xing Zhu, Ming-Quan Qian
Previous studies have demonstrated that G-protein coupled receptor kinase interacting protein-1 (GIT1) and microRNAs (miRNAs) serve an important role in chondrocyte proliferation and migration. However, a limited number of studies conducted thus far have investigated the association between GIT1 and miRNAs. In the present study, putative miR‑195 binding sites in the GIT1 3'‑untranslated region were identified using common bioinformatic algorithms (miRanda, TargetScan, miRBase and miRWalk), and it was demonstrated that they may be involved in regulating GIT1 expression...
January 2017: Molecular Medicine Reports
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