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PubMed Journals Articles About "Receptor Tyrosine Protein Kinase ERBB Global Market Research" RSS

18:43 EDT 17th September 2019 | BioPortfolio

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Showing "Receptor Tyrosine Protein Kinase ERBB Global Market Research" PubMed Articles 1–25 of 47,000+

Resolving the Conformational Dynamics of ErbB Growth Factor Receptor Dimers.

The combinatorial dimerization of the ErbB growth factor receptors (ErbB- ErbB) are critical for their function. Here, we have characterized the conformational dynamics of ErbB transmembrane homo-dimers and hetero-dimers by using a coarse-grain simulation framework. All dimers, except ErbB and ErbB, exhibit at least two conformations. The reported NMR structures correspond to one of these conformations representing the N-terminal active state in ErbB (RH2), ErbB (RH1) and ErbB (RH) homo-dimers and the LH di...


Crystal structure of the SH3 domain of human Lyn non-receptor tyrosine kinase.

Lyn kinase (Lck/Yes related novel protein tyrosine kinase) belongs to the family of Src-related non-receptor tyrosine kinases. Consistent with physiological roles in cell growth and proliferation, aberrant function of Lyn is associated with various forms of cancer, including leukemia, breast cancer and melanoma. Here, we determine a 1.3 Å resolution crystal structure of the polyproline-binding SH3 regulatory domain of human Lyn kinase, which adopts a five-stranded β-barrel fold. Mapping of cancer-associat...

Protein kinase C regulates ErbB3 turnover.

ErbB3, which belongs to the epidermal growth factor receptor (EGFR) or ErbB family of receptor tyrosine kinases, is involved in progression of several human cancers and a tight regulation of its expression is crucial. An important mechanism for regulation of ErbB proteins is endocytosis and we recently showed that ErbB3, contrary to other ErbB proteins, like EGFR and ErbB2, is constitutively internalized and degraded. Several studies show that protein kinase C (PKC) can regulate the activation, localization...


Receptor tyrosine kinase activation induces free fatty acid 4 receptor phosphorylation, β-arrestin interaction, and internalization.

FFA4 (Free Fatty Acid receptor 4, previously known as GPR120) is a G protein-coupled receptor that acts as a sensor of long-chain fatty acids, modulates metabolism, and whose dysfunction participates in endocrine disturbances. FFA4 is known to be phosphorylated and internalized in response to agonists and protein kinase C activation. In this paper report the modulation of this fatty acid receptor by activation of receptor tyrosine kinases. Cell-activation with growth factors (insulin, epidermal growth facto...

Selective Proteolysis to Study the Global Conformation and Regulatory Mechanisms of c-Src Kinase.

Protein kinase pathways are traditionally mapped by monitoring downstream phosphorylation. Meanwhile, the noncatalytic functions of protein kinases remain under-appreciated as critical components of kinase signaling. c-Src is a protein kinase known to have noncatalytic signaling function important in healthy and disease cell signaling. Large conformational changes in the regulatory domains regulate c-Src's noncatalytic functions. Herein, we demonstrate that changes in the global conformation of c-Src can be...

Grb7, a Critical Mediator of EGFR/ErbB Signaling, in Cancer Development and as a Potential Therapeutic Target.

The partner of activated epidermal growth factor receptor (EGFR), growth factor receptor bound protein-7 (Grb7), a functionally multidomain adaptor protein, has been demonstrated to be a pivotal regulator for varied physiological and pathological processes by interacting with phospho-tyrosine-related signaling molecules to affect the transmission through a number of signaling pathways. In particular, critical roles of Grb7 in erythroblastic leukemia viral oncogene homolog (ERBB) family-mediated cancer devel...

Effect of Metformin Plus Tyrosine Kinase Inhibitors Compared With Tyrosine Kinase Inhibitors Alone in Patients With Epidermal Growth Factor Receptor-Mutated Lung Adenocarcinoma: A Phase 2 Randomized Clinical Trial.

Metformin hydrochloride is emerging as a repurposed anticancer drug. Preclinical and retrospective studies have shown that it improves outcomes across a wide variety of neoplasms, including lung cancer. Particularly, evidence is accumulating regarding the synergistic association between metformin and epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs).

Prognostic value of receptor tyrosine kinase-like orphan receptor (ROR) family in cancer: A meta-analysis.

Identification of membrane proteins expressed exclusively on tumor cells is a goal for cancer drug development. The receptor tyrosine kinase-like orphan receptor type 1 and 2 (ROR1/2), are type-I transmembrane proteins expressed in cancer but not in adult normal tissue. Here, we explore the prognostic role ROR1/2 expression on patient outcome.

Tyrosine kinase Eph receptor A6 sensitizes glioma-initiating cells towards bone morphogenetic protein-induced apoptosis.

Bone morphogenetic protein (BMP) signaling plays important roles in glioblastoma multiforme (GBM), a lethal form of brain tumor. BMPs reduce GBM tumorigenicity through its differentiation- and apoptosis-inducing effects on glioma-initiating cells (GICs). However, some GICs do not respond to the tumor suppressive effects of BMPs. Using a phospho-receptor tyrosine kinase array, we found that EPHA6 (erythropoietin-producing hepatocellular carcinoma receptor A6) phosphorylation was regulated by BMP-2 signaling ...

Purification and characterization of the extracellular region of human receptor tyrosine kinase like orphan receptor 2 (ROR2).

Receptor tyrosine kinase like orphan receptor 2 (ROR2) is a co-receptor for some Wnt proteins including Wnt5a that activate the noncanonical Wnt/planar cell polarity (PCP) signaling pathway. Upregulation of ROR2 is associated with several cancer forms. The extracellular region of ROR2, which contains an immunoglobulin (Ig)-like domain, a Frizzled like cysteine-rich domain (CRD) and a Kringle domain, is a potential anticancer drug target. The structural and biochemical properties of the ROR2 extracellular re...

Efficacy and Safety of ALK Tyrosine Kinase Inhibitors in Elderly Patients with Advanced ALK-Positive Non-Small Cell Lung Cancer: Findings from the Real-Life Cohort.

Little is known regarding the anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor (TKI) efficacy and safety in the elderly.

Association of radiomic features with epidermal growth factor receptor mutation status in non-small cell lung cancer and survival treated with tyrosine kinase inhibitors.

Since the discovery of the fact that tyrosine kinase inhibitors could improve progression-free survival for patients with advanced non-small cell lung cancer compared with traditional chemotherapy, it has been extremely important to identify epidermal growth factor receptor mutation status in treatment stratification. Although lack of sufficient biopsy samples limit the precise detection of epidermal growth factor receptor mutation status in clinical practice, and it is difficult to identify the sensitive p...

Discovery of Branebrutinib (BMS-986195): A Strategy for Identifying a Highly Potent and Selective Covalent Inhibitor Providing Rapid In Vivo Inactivation of Bruton's Tyrosine Kinase (BTK).

Bruton's tyrosine kinase (BTK), a non-receptor tyrosine kinase, is a member of the Tec family of kinases and is essential for B cell receptor (BCR)-mediated signaling. BTK also plays a critical role in the downstream signaling pathways for the Fc-gamma receptor in monocytes, the Fc-epsilon receptor in granulocytes, and the RANK receptor in osteoclasts. As a result, pharmacological inhibition of BTK is anticipated to provide an effective strategy for the clinical treatment of autoimmune diseases such as rheu...

Tumor tissue and plasma levels of AXL and GAS6 before and after tyrosine kinase inhibitor treatment in EGFR-mutated non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) positive for activating mutations of the epidermal growth factor receptor (EGFR) gene is initially sensitive to EGFR-tyrosine kinase inhibitors (TKIs) but eventually develops resistance to these drugs. Upregulation of the receptor tyrosine kinase AXL in tumor tissue has been detected in about one-fifth of NSCLC patients with acquired resistance to EGFR-TKIs. However, the clinical relevance of the levels of AXL and its ligand GAS6 in plasma remains unknown.

Hypoglycemia causes dysregulation of Neuregulin 1, ErbB receptors, Ki67 in cerebellum and brainstem during diabetes: Implications in motor function.

Hypoglycemia induced brain injury poses a major setback to optimal blood glucose regulation during diabetes. It causes irreversible injury in several brain regions culminating in improper function. Neuregulin 1 and ErbB receptors are involved in regeneration in adulthood as well as in glucose homeostasis. We intended to understand the influence of extreme discrepancies in glycemic levels on Neuregulin 1, ErbB receptor subtypes and Ki67 expression in relation to motor deficits as a consequence of cellular dy...

Identification of the Direct Substrates of the ABL Kinase via Kinase Assay Linked Phosphoproteomics with Multiple Drug Treatments.

Ableson tyrosine kinase (ABL) plays an essential role in cell differentiation, division, adhesion, and stress response. However, the mutant fusion BCR-ABL has constitutive kinase activity that causes chronic myelogenous leukemia (CML). Small molecule tyrosine kinase inhibitors (TKIs) such as imatinib revolutionized the treatment of CML and other cancers, but acquired resistance to these inhibitors, even second-generation TKIs, is rising. Thus, careful dissection of ABL signaling pathways is needed to find n...

Hydroxyl-Rich PGMA-Based Cationic Glycopolymers for Intracellular siRNA Delivery: Biocompatibility and Effect of Sugar Decoration Degree.

The ErbB family of proteins, structurally related to the epidermal growth factor receptor (EGFR), is found to be over-expressed in many cancers such as gliomas, lung and cervical carcinomas. Gene therapy allows to modify the expression of genes like ErbB and has been a promising strategy to target oncogenes and tumor suppressor genes. In the current work, novel hydroxyl-rich polyglycidyl methacrylate (PGMA)-based cationic glycopolymers were designed for intracellular small interfering RNA (siRNA) delivery t...

Neuregulin-1/ErbB Network: An Emerging Modulator of Nervous System Injury and Repair.

Neuregulin-1 (Nrg-1) is a member of the Neuregulin family of growth factors with essential roles in the developing and adult nervous system. Six different types of Nrg-1 (Nrg-1 type I-VI) and over 30 isoforms have been discovered; however, their specific roles are not fully determined. Nrg-1 signals through a complex network of protein-tyrosine kinase receptors, ErbB2, ErbB3, ErbB4 and multiple intracellular pathways. Genetic and pharmacological studies of Nrg-1 and ErbB receptors have identified a critical...

Properties of FDA-approved small molecule protein kinase inhibitors.

Because mutations, overexpression, and dysregulation of protein kinases play essential roles in the pathogenesis of many illnesses, this enzyme family has become one of the most important drug targets in the past 20 years. The US FDA has approved 48 small molecule protein kinase inhibitors, nearly all of which are orally effective with the exceptions of netarsudil (which is given as an eye drop) and temsirolimus (which is given intravenously). Of the 48 approved drugs, the majority (25) target receptor prot...

Molecular Mechanisms of Tyrosine Kinase Inhibitor Resistance Induced by Membranous/Cytoplasmic/Nuclear Translocation of Epidermal Growth Factor Receptor.

The molecular mechanism underlying the induction of resistance to tyrosine kinase inhibitors (TKIs) via the membranous/cytoplasmic/nuclear translocation of epidermal growth factor receptor (EGFR) has not yet been reported.

Measuring GPCR-Induced Activation of Protein Tyrosine Phosphatases (PTP) Using In-Gel and Colorimetric PTP Assays.

Given the increasing amount of data showing the importance of protein tyrosine phosphatases (PTPs) in G protein-coupled receptor (GPCR) signaling pathways, the modulation of this enzyme family by that type of receptor can become an important experimental question. Here, we describe two different methods, an in-gel and a colorimetric PTP assay, to evaluate the modulation of PTP activity after stimulation with GPCR agonists.

Mechanisms of ERBB3 Action in Human Neoplasia.

It is well established that the epidermal growth factor receptor, ERBB2/HER2 and, to a lesser extent, ERBB4/HER4 promote the pathogenesis of many types of human cancers. In contrast, the role that ERBB3/HER3, the fourth member of the ERBB family of receptor tyrosine kinases, plays in these diseases is poorly understood and, until recently, underappreciated. In large part, this was because early structural and functional studies suggested that ERBB3 had little, if any, intrinsic tyrosine kinase activity and ...

Next-generation Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors for Leptomeningeal Carcinomatosis: Review of 2 Cases.

Epidermal growth factor receptor (EGFR) mutation status is strongly correlated with leptomeningeal carcinomatosis in non-small cell lung cancer. Historically, patients were treated with radiotherapy, intrathecal chemotherapy or first-generation EGFR tyrosine kinase inhibitors (TKIs); however, most would eventually develop resistance and disease progression. Therefore, recent interest has sparked in investigating next-generation EGFR-TKI monotherapy.

Natural products as important tyrosine kinase inhibitors.

As an important source of drugs, natural products play an important role in the discovery and development of new drugs. More than 60% of anti-tumor drugs are closely related to natural products. At the same time, as the main cause of tumors, the abnormal activity of tyrosine kinase has become an important target for clinical treatment. Although, small molecule targeted drugs dominate the cancer treatment. Natural active products are driving the development of new tyrosine kinase inhibitors with their unique...

A course-based undergraduate research experience in biochemistry that is suitable for students with various levels of preparedness.

Due to resource limitations at predominantly undergraduate institutions, research opportunities for non-senior students can be limited. To provide opportunities for a variety of students to gain exposure to research, a course-based undergraduate research experience (CURE) was designed and conducted. Coupled inquiry was used to allow underclassmen and upperclassmen to participate. Students first utilized a bioinformatics approach to develop hypotheses concerning protein interactions with the receptor Mer tyr...


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