Special Issue "Receptor Tyrosine Kinases in Health and Disease"

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cell Signaling and Regulated Cell Death".

Deadline for manuscript submissions: 28 February 2019

Special Issue Editor

Guest Editor
Prof. Dr. Ichiro Maruyama

Okinawa Institute of Science and Technology Graduate University, 1919-1 Tancha, Onna, Kunigami, Okinawa 904-0495, Japan
Website | E-Mail
Interests: cell surface receptors; transmembrane signaling; receptor tyrosine kinases; learning and memory; decision-making; animal behavior

Special Issue Information

Dear Colleagues

Receptor tyrosine kinases (RTKs) play essential roles in cellular processes, including metabolism, cell-cycle control, survival, proliferation, motility and differentiation. RTKs are all synthesized as single-pass transmembrane proteins and bind polypeptide ligands, mainly growth factors. There are a number of mechanisms by which the tight regulation of TRK signaling can be abrogated, including enhanced production of ligands, overproduction of TRK proteins, mutations leading constitutive activation of TRK, deficiency of TRK downregulation, and activation of TRK through cross-talk with heterologous cell-surface receptors. Dysregulation of these processes directly links to disease in humans. Small molecule inhibitors are widely used that can target RTK functionality in disease. Antibodies that inhibit RTKs have also been developed, and are in current use or development in the clinic.

The aim of this Special Issues of Cells is to offer an Open Access collection of reviews on forefront research on RTKs that covers all the above aspects.

Prof. Dr. Ichiro Maruyama
Guest Editor

 

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cells is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1000 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • anti-tumor drug
  • cancer
  • developmental syndrome
  • domain
  • growth factor
  • kinome
  • mental disorder
  • monoclonal antibody
  • nanobody
  • phosphorylation
  • preformed dimer
  • receptor tyrosine kinase
  • signal transduction
  • small chemical inhibitor
  • transmembrane signaling
  • tumor

Published Papers (4 papers)

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Review

Open AccessFeature PaperReview Current Status of Fibroblast Growth Factor Receptor-Targeted Therapies in Breast Cancer
Received: 5 June 2018 / Revised: 30 June 2018 / Accepted: 11 July 2018 / Published: 15 July 2018
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Abstract
Breast cancer (BC) is the most common malignancy and second only to lung cancer in terms of mortality in women. Despite the incredible progress made in this field, metastatic breast cancer has a poor prognosis. In an era of personalized medicine, there is
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Breast cancer (BC) is the most common malignancy and second only to lung cancer in terms of mortality in women. Despite the incredible progress made in this field, metastatic breast cancer has a poor prognosis. In an era of personalized medicine, there is an urgent need for better knowledge of the biology leading to the disease, which can lead to the design of increasingly accurate drugs against patients’ specific molecular aberrations. Among one of the actionable targets is the fibroblast growth factor receptor (FGFR) pathway, triggered by specific ligands. The Fibroblast Growth Factor Receptors/Fibroblast Growth Factors (FGFRs/FGFs) axis offers interesting molecular targets to be pursued in clinical development. This mini-review will focus on the current knowledge of FGFR mutations, which lead to tumor formation and summarizes the state-of-the-art therapeutic strategies for targeted treatments against the FGFRs/FGFs axis in the context of BC. Full article
(This article belongs to the Special Issue Receptor Tyrosine Kinases in Health and Disease)
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Open AccessFeature PaperReview Receptor Tyrosine Kinase Ubiquitination and De-Ubiquitination in Signal Transduction and Receptor Trafficking
Received: 13 February 2018 / Revised: 9 March 2018 / Accepted: 13 March 2018 / Published: 15 March 2018
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Abstract
Receptor tyrosine kinases (RTKs) are membrane-based sensors that enable rapid communication between cells and their environment. Evidence is now emerging that interdependent regulatory mechanisms, such as membrane trafficking, ubiquitination, proteolysis and gene expression, have substantial effects on RTK signal transduction and cellular responses.
[...] Read more.
Receptor tyrosine kinases (RTKs) are membrane-based sensors that enable rapid communication between cells and their environment. Evidence is now emerging that interdependent regulatory mechanisms, such as membrane trafficking, ubiquitination, proteolysis and gene expression, have substantial effects on RTK signal transduction and cellular responses. Different RTKs exhibit both basal and ligand-stimulated ubiquitination, linked to trafficking through different intracellular compartments including the secretory pathway, plasma membrane, endosomes and lysosomes. The ubiquitin ligase superfamily comprising the E1, E2 and E3 enzymes are increasingly implicated in this post-translational modification by adding mono- and polyubiquitin tags to RTKs. Conversely, removal of these ubiquitin tags by proteases called de-ubiquitinases (DUBs) enables RTK recycling for another round of ligand sensing and signal transduction. The endocytosis of basal and activated RTKs from the plasma membrane is closely linked to controlled proteolysis after trafficking and delivery to late endosomes and lysosomes. Proteolytic RTK fragments can also have the capacity to move to compartments such as the nucleus and regulate gene expression. Such mechanistic diversity now provides new opportunities for modulating RTK-regulated cellular responses in health and disease states. Full article
(This article belongs to the Special Issue Receptor Tyrosine Kinases in Health and Disease)
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Open AccessReview Targeting FLT3 Mutations in Acute Myeloid Leukemia
Received: 30 October 2017 / Revised: 19 December 2017 / Accepted: 4 January 2018 / Published: 8 January 2018
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Abstract
The FMS-like tyrosine kinase 3 (FLT3) pathway has an important role in cellular proliferation, survival, and differentiation. Acute myeloid leukemia (AML) patients with mutated FLT3 have a large disease burden at presentation and a dismal prognosis. A number of FLT3 inhibitors have been
[...] Read more.
The FMS-like tyrosine kinase 3 (FLT3) pathway has an important role in cellular proliferation, survival, and differentiation. Acute myeloid leukemia (AML) patients with mutated FLT3 have a large disease burden at presentation and a dismal prognosis. A number of FLT3 inhibitors have been developed over the years. The first-generation inhibitors are largely non-specific, while the second-generation inhibitors are more specific and more potent. These inhibitors are used to treat patients with FLT3-mutated AML in virtually all disease settings including induction, consolidation, maintenance, relapse, and after hematopoietic cell transplantation (HCT). In this article, we will review the use of FLT3 inhibitors in AML. Full article
(This article belongs to the Special Issue Receptor Tyrosine Kinases in Health and Disease)
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Open AccessFeature PaperReview Activation of the EGF Receptor by Ligand Binding and Oncogenic Mutations: The “Rotation Model”
Received: 21 April 2017 / Revised: 17 May 2017 / Accepted: 31 May 2017 / Published: 2 June 2017
Cited by 7 | PDF Full-text (1510 KB) | HTML Full-text | XML Full-text
Abstract
The epidermal growth factor receptor (EGFR) plays vital roles in cellular processes including cell proliferation, survival, motility, and differentiation. The dysregulated activation of the receptor is often implicated in human cancers. EGFR is synthesized as a single-pass transmembrane protein, which consists of an
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The epidermal growth factor receptor (EGFR) plays vital roles in cellular processes including cell proliferation, survival, motility, and differentiation. The dysregulated activation of the receptor is often implicated in human cancers. EGFR is synthesized as a single-pass transmembrane protein, which consists of an extracellular ligand-binding domain and an intracellular kinase domain separated by a single transmembrane domain. The receptor is activated by a variety of polypeptide ligands such as epidermal growth factor and transforming growth factor α. It has long been thought that EGFR is activated by ligand-induced dimerization of the receptor monomer, which brings intracellular kinase domains into close proximity for trans-autophosphorylation. An increasing number of diverse studies, however, demonstrate that EGFR is present as a pre-formed, yet inactive, dimer prior to ligand binding. Furthermore, recent progress in structural studies has provided insight into conformational changes during the activation of a pre-formed EGFR dimer. Upon ligand binding to the extracellular domain of EGFR, its transmembrane domains rotate or twist parallel to the plane of the cell membrane, resulting in the reorientation of the intracellular kinase domain dimer from a symmetric inactive configuration to an asymmetric active form (the “rotation model”). This model is also able to explain how oncogenic mutations activate the receptor in the absence of the ligand, without assuming that the mutations induce receptor dimerization. In this review, we discuss the mechanisms underlying the ligand-induced activation of the preformed EGFR dimer, as well as how oncogenic mutations constitutively activate the receptor dimer, based on the rotation model. Full article
(This article belongs to the Special Issue Receptor Tyrosine Kinases in Health and Disease)
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