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Tyrosine Kinases in Health and Disease
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Tyrosine Kinases in Health and Disease

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (31 January 2021) | Viewed by 25058

Special Issue Editors

Prof. Dr. Arkadiusz Orzechowski

E-Mail Website
Guest Editor
Department of Physiological Sciences, Institute of Veterinary Medicine, Warsaw University of Life Sciences—SGGW, Nowoursynowska 159, 02-776 Warsaw, Poland
Interests: skeletal muscle; muscle cachexia; cyto- and myokines; kinases; autophagy; apoptosis; lipid rafts; cholesterol; isoprenoids; Alzheimer's disease
Special Issues, Collections and Topics in MDPI journals
Dr. Katarzyna Grzelkowska-Kowalczyk

E-Mail Website
Guest Editor
Department of Physiological Sciences, Institute of Veterinary Medicine, Warsaw University of Life Sciences (SGGW), Nowoursynowska 159, 02-776 Warsaw, Poland
Interests: cell biology; molecular biology; cell signaling; protein kinases; microRNA; transcriptome profiling; cell proliferation and differentiation; myogenesis; skeletal muscle growth and regeneration; skeletal muscle secretome; adipogenesis; obesity; adipokines; insulin resistance

Special Issue Information

Dear Colleagues,

Tyrosine kinases (TKs) represent a group of enzymes that add the phosphate group from ATP to the target hydroxyl group in tyrosines of selected proteins. Resulting phosphotyrosines are attractive residues for proteins with protein tyrosine binding domains (SH2, SH3). There are two distinct groups of TKs, namely, receptor tyrosine kinases (RTKs, 20 subfamilies) and non-receptor tyrosine kinases (NRTKs, 9 subfamilies). Altogether, at least 90 different TKs are known in human kinome which consists of 500 kinases. TKs transduce the extracellular signal to cells in order to evoke a physiological response to stimulus. This response is fundamental for cell growth, differentiation, migration, metabolism or to overcome the programmed cell death. Overall phosphotyrosines (with few exceptions) herald the “green light” for trophic reactions. Tyrosine kinases control homeostasis but when overexcited lead to tumorigenesis. TKs represent a large group of oncogenes that for last decades were subjected to successful inhibition with pharmacological approaches including natural compounds. This Special Issue is dedicated to submissions addressing the TKs in health and disease.

Prof. Dr. Arkadiusz Orzechowski
Dr. Katarzyna Grzelkowska-Kowalczyk
Guest Editors

Manuscript Submission Information

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Keywords

  • Tyrosine kinases
  • Phosphotyrosines
  • Growth
  • Oncogenes
  • Neoplasia
  • Malignancy

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Published Papers (5 papers)

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20 pages, 4630 KiB  
Article
Single-Molecule Super-Resolution Microscopy Reveals Heteromeric Complexes of MET and EGFR upon Ligand Activation
by Marie-Lena I.E. Harwardt, Mark S. Schröder, Yunqing Li, Sebastian Malkusch, Petra Freund, Shashi Gupta, Nebojsa Janjic, Sebastian Strauss, Ralf Jungmann, Marina S. Dietz and Mike Heilemann
Int. J. Mol. Sci. 2020, 21(8), 2803; https://doi.org/10.3390/ijms21082803 - 17 Apr 2020
Cited by 26 | Viewed by 4972
Abstract
Receptor tyrosine kinases (RTKs) orchestrate cell motility and differentiation. Deregulated RTKs may promote cancer and are prime targets for specific inhibitors. Increasing evidence indicates that resistance to inhibitor treatment involves receptor cross-interactions circumventing inhibition of one RTK by activating alternative signaling pathways. Here, [...] Read more.
Receptor tyrosine kinases (RTKs) orchestrate cell motility and differentiation. Deregulated RTKs may promote cancer and are prime targets for specific inhibitors. Increasing evidence indicates that resistance to inhibitor treatment involves receptor cross-interactions circumventing inhibition of one RTK by activating alternative signaling pathways. Here, we used single-molecule super-resolution microscopy to simultaneously visualize single MET and epidermal growth factor receptor (EGFR) clusters in two cancer cell lines, HeLa and BT-20, in fixed and living cells. We found heteromeric receptor clusters of EGFR and MET in both cell types, promoted by ligand activation. Single-protein tracking experiments in living cells revealed that both MET and EGFR respond to their cognate as well as non-cognate ligands by slower diffusion. In summary, for the first time, we present static as well as dynamic evidence of the presence of heteromeric clusters of MET and EGFR on the cell membrane that correlates with the relative surface expression levels of the two receptors. Full article
(This article belongs to the Special Issue Tyrosine Kinases in Health and Disease)
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Review

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14 pages, 4358 KiB  
Review
Pancreatic Adenocarcinoma Therapeutics Targeting RTK and TGF Beta Receptor
by Hsin-Han Yang, Jen-Wei Liu, Jui-Hao Lee, Horng-Jyh Harn and Tzyy-Wen Chiou
Int. J. Mol. Sci. 2021, 22(15), 8125; https://doi.org/10.3390/ijms22158125 - 29 Jul 2021
Cited by 15 | Viewed by 4273
Abstract
Despite the improved overall survival rates in most cancers, pancreatic cancer remains one of the deadliest cancers in this decade. The rigid microenvironment, which majorly comprises cancer-associated fibroblasts (CAFs), plays an important role in the obstruction of pancreatic cancer therapy. To overcome this [...] Read more.
Despite the improved overall survival rates in most cancers, pancreatic cancer remains one of the deadliest cancers in this decade. The rigid microenvironment, which majorly comprises cancer-associated fibroblasts (CAFs), plays an important role in the obstruction of pancreatic cancer therapy. To overcome this predicament, the signaling of receptor tyrosine kinases (RTKs) and TGF beta receptor (TGFβR) in both pancreatic cancer cell and supporting CAF should be considered as the therapeutic target. The activation of receptors has been reported to be aberrant to cell cycle regulation, and signal transduction pathways, such as growth-factor induced proliferation, and can also influence the apoptotic sensitivity of tumor cells. In this article, the regulation of RTKs/TGFβR between pancreatic ductal adenocarcinoma (PDAC) and CAFs, as well as the RTKs/TGFβR inhibitor-based clinical trials on pancreatic cancer are reviewed. Full article
(This article belongs to the Special Issue Tyrosine Kinases in Health and Disease)
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16 pages, 1021 KiB  
Review
Lemur Tyrosine Kinases and Prostate Cancer: A Literature Review
by Elena Ferrari, Valeria Naponelli and Saverio Bettuzzi
Int. J. Mol. Sci. 2021, 22(11), 5453; https://doi.org/10.3390/ijms22115453 - 21 May 2021
Cited by 3 | Viewed by 2828
Abstract
The members of the Lemur Tyrosine Kinases (LMTK1-3) subfamily constitute a group of three membrane-anchored kinases. They are known to influence a wide variety of key cellular events, often affecting cell proliferation and apoptosis. They have been discovered to be involved in cancer, [...] Read more.
The members of the Lemur Tyrosine Kinases (LMTK1-3) subfamily constitute a group of three membrane-anchored kinases. They are known to influence a wide variety of key cellular events, often affecting cell proliferation and apoptosis. They have been discovered to be involved in cancer, in that they impact various signalling pathways that influence cell proliferation, migration, and invasiveness. Notably, in the context of genome-wide association studies, one member of the LMTK family has been identified as a candidate gene which could contribute to the development of prostate cancer. In this review, of published literature, we present evidence on the role of LMTKs in human prostate cancer and model systems, focusing on the complex network of interacting partners involved in signalling cascades that are frequently activated in prostate cancer malignancy. We speculate that the modulators of LMTK enzyme expression and activity would be of high clinical relevance for the design of innovative prostate cancer treatment. Full article
(This article belongs to the Special Issue Tyrosine Kinases in Health and Disease)
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48 pages, 965 KiB  
Review
Tyrosine Kinase Receptors in Oncology
by Jorge Esteban-Villarrubia, Juan José Soto-Castillo, Javier Pozas, María San Román-Gil, Inmaculada Orejana-Martín, Javier Torres-Jiménez, Alfredo Carrato, Teresa Alonso-Gordoa and Javier Molina-Cerrillo
Int. J. Mol. Sci. 2020, 21(22), 8529; https://doi.org/10.3390/ijms21228529 - 12 Nov 2020
Cited by 53 | Viewed by 6040
Abstract
Tyrosine kinase receptors (TKR) comprise more than 60 molecules that play an essential role in the molecular pathways, leading to cell survival and differentiation. Consequently, genetic alterations of TKRs may lead to tumorigenesis and, therefore, cancer development. The discovery and improvement of tyrosine [...] Read more.
Tyrosine kinase receptors (TKR) comprise more than 60 molecules that play an essential role in the molecular pathways, leading to cell survival and differentiation. Consequently, genetic alterations of TKRs may lead to tumorigenesis and, therefore, cancer development. The discovery and improvement of tyrosine kinase inhibitors (TKI) against TKRs have entailed an important step in the knowledge-expansion of tumor physiopathology as well as an improvement in the cancer treatment based on molecular alterations over many tumor types. The purpose of this review is to provide a comprehensive review of the different families of TKRs and their role in the expansion of tumor cells and how TKIs can stop these pathways to tumorigenesis, in combination or not with other therapies. The increasing growth of this landscape is driving us to strengthen the development of precision oncology with clinical trials based on molecular-based therapy over a histology-based one, with promising preliminary results. Full article
(This article belongs to the Special Issue Tyrosine Kinases in Health and Disease)
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14 pages, 1106 KiB  
Review
Nuclear Functions of the Tyrosine Kinase Src
by Giulia Bagnato, Martina Leopizzi, Enrica Urciuoli and Barbara Peruzzi
Int. J. Mol. Sci. 2020, 21(8), 2675; https://doi.org/10.3390/ijms21082675 - 11 Apr 2020
Cited by 31 | Viewed by 6138
Abstract
Src is the representative member of the Src-family kinases (SFKs), a group of tyrosine kinases involved in several cellular processes. Its main function has been for long confined to the plasma membrane/cytoplasm compartment, being a myristoylated protein anchored to the cell membrane and [...] Read more.
Src is the representative member of the Src-family kinases (SFKs), a group of tyrosine kinases involved in several cellular processes. Its main function has been for long confined to the plasma membrane/cytoplasm compartment, being a myristoylated protein anchored to the cell membrane and functioning downstream to receptors, most of them lacking intrinsic kinase activity. In the last decades, new roles for some SFKs have been described in the nuclear compartment, suggesting that these proteins can also be involved in directly regulating gene transcription or nucleoskeleton architecture. In this review, we focused on those nuclear functions specifically attributable to Src, by considering its function as both tyrosine kinase and adapting molecule. In particular, we addressed the Src involvement in physiological as well as in pathological conditions, especially in tumors. Full article
(This article belongs to the Special Issue Tyrosine Kinases in Health and Disease)
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