Cargando…

Role of Non Receptor Tyrosine Kinases in Hematological Malignances and its Targeting by Natural Products

Tyrosine kinases belong to a family of enzymes that mediate the movement of the phosphate group to tyrosine residues of target protein, thus transmitting signals from the cell surface to cytoplasmic proteins and the nucleus to regulate physiological processes. Non-receptor tyrosine kinases (NRTK) ar...

Descripción completa

Detalles Bibliográficos
Autores principales: Siveen, Kodappully S., Prabhu, Kirti S., Achkar, Iman W., Kuttikrishnan, Shilpa, Shyam, Sunitha, Khan, Abdul Q., Merhi, Maysaloun, Dermime, Said, Uddin, Shahab
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5817858/
https://www.ncbi.nlm.nih.gov/pubmed/29455667
http://dx.doi.org/10.1186/s12943-018-0788-y
_version_ 1783300941090390016
author Siveen, Kodappully S.
Prabhu, Kirti S.
Achkar, Iman W.
Kuttikrishnan, Shilpa
Shyam, Sunitha
Khan, Abdul Q.
Merhi, Maysaloun
Dermime, Said
Uddin, Shahab
author_facet Siveen, Kodappully S.
Prabhu, Kirti S.
Achkar, Iman W.
Kuttikrishnan, Shilpa
Shyam, Sunitha
Khan, Abdul Q.
Merhi, Maysaloun
Dermime, Said
Uddin, Shahab
author_sort Siveen, Kodappully S.
collection PubMed
description Tyrosine kinases belong to a family of enzymes that mediate the movement of the phosphate group to tyrosine residues of target protein, thus transmitting signals from the cell surface to cytoplasmic proteins and the nucleus to regulate physiological processes. Non-receptor tyrosine kinases (NRTK) are a sub-group of tyrosine kinases, which can relay intracellular signals originating from extracellular receptor. NRTKs can regulate a huge array of cellular functions such as cell survival, division/propagation and adhesion, gene expression, immune response, etc. NRTKs exhibit considerable variability in their structural make up, having a shared kinase domain and commonly possessing many other domains such as SH2, SH3 which are protein-protein interacting domains. Recent studies show that NRTKs are mutated in several hematological malignancies, including lymphomas, leukemias and myelomas, leading to aberrant activation. It can be due to point mutations which are intragenic changes or by fusion of genes leading to chromosome translocation. Mutations that lead to constitutive kinase activity result in the formation of oncogenes, such as Abl, Fes, Src, etc. Therefore, specific kinase inhibitors have been sought after to target mutated kinases. A number of compounds have since been discovered, which have shown to inhibit the activity of NRTKs, which are remarkably well tolerated. This review covers the role of various NRTKs in the development of hematological cancers, including their deregulation, genetic alterations, aberrant activation and associated mutations. In addition, it also looks at the recent advances in the development of novel natural compounds that can target NRTKs and perhaps in combination with other forms of therapy can show great promise for the treatment of hematological malignancies.
format Online
Article
Text
id pubmed-5817858
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-58178582018-02-23 Role of Non Receptor Tyrosine Kinases in Hematological Malignances and its Targeting by Natural Products Siveen, Kodappully S. Prabhu, Kirti S. Achkar, Iman W. Kuttikrishnan, Shilpa Shyam, Sunitha Khan, Abdul Q. Merhi, Maysaloun Dermime, Said Uddin, Shahab Mol Cancer Review Tyrosine kinases belong to a family of enzymes that mediate the movement of the phosphate group to tyrosine residues of target protein, thus transmitting signals from the cell surface to cytoplasmic proteins and the nucleus to regulate physiological processes. Non-receptor tyrosine kinases (NRTK) are a sub-group of tyrosine kinases, which can relay intracellular signals originating from extracellular receptor. NRTKs can regulate a huge array of cellular functions such as cell survival, division/propagation and adhesion, gene expression, immune response, etc. NRTKs exhibit considerable variability in their structural make up, having a shared kinase domain and commonly possessing many other domains such as SH2, SH3 which are protein-protein interacting domains. Recent studies show that NRTKs are mutated in several hematological malignancies, including lymphomas, leukemias and myelomas, leading to aberrant activation. It can be due to point mutations which are intragenic changes or by fusion of genes leading to chromosome translocation. Mutations that lead to constitutive kinase activity result in the formation of oncogenes, such as Abl, Fes, Src, etc. Therefore, specific kinase inhibitors have been sought after to target mutated kinases. A number of compounds have since been discovered, which have shown to inhibit the activity of NRTKs, which are remarkably well tolerated. This review covers the role of various NRTKs in the development of hematological cancers, including their deregulation, genetic alterations, aberrant activation and associated mutations. In addition, it also looks at the recent advances in the development of novel natural compounds that can target NRTKs and perhaps in combination with other forms of therapy can show great promise for the treatment of hematological malignancies. BioMed Central 2018-02-19 /pmc/articles/PMC5817858/ /pubmed/29455667 http://dx.doi.org/10.1186/s12943-018-0788-y Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Review
Siveen, Kodappully S.
Prabhu, Kirti S.
Achkar, Iman W.
Kuttikrishnan, Shilpa
Shyam, Sunitha
Khan, Abdul Q.
Merhi, Maysaloun
Dermime, Said
Uddin, Shahab
Role of Non Receptor Tyrosine Kinases in Hematological Malignances and its Targeting by Natural Products
title Role of Non Receptor Tyrosine Kinases in Hematological Malignances and its Targeting by Natural Products
title_full Role of Non Receptor Tyrosine Kinases in Hematological Malignances and its Targeting by Natural Products
title_fullStr Role of Non Receptor Tyrosine Kinases in Hematological Malignances and its Targeting by Natural Products
title_full_unstemmed Role of Non Receptor Tyrosine Kinases in Hematological Malignances and its Targeting by Natural Products
title_short Role of Non Receptor Tyrosine Kinases in Hematological Malignances and its Targeting by Natural Products
title_sort role of non receptor tyrosine kinases in hematological malignances and its targeting by natural products
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5817858/
https://www.ncbi.nlm.nih.gov/pubmed/29455667
http://dx.doi.org/10.1186/s12943-018-0788-y
work_keys_str_mv AT siveenkodappullys roleofnonreceptortyrosinekinasesinhematologicalmalignancesanditstargetingbynaturalproducts
AT prabhukirtis roleofnonreceptortyrosinekinasesinhematologicalmalignancesanditstargetingbynaturalproducts
AT achkarimanw roleofnonreceptortyrosinekinasesinhematologicalmalignancesanditstargetingbynaturalproducts
AT kuttikrishnanshilpa roleofnonreceptortyrosinekinasesinhematologicalmalignancesanditstargetingbynaturalproducts
AT shyamsunitha roleofnonreceptortyrosinekinasesinhematologicalmalignancesanditstargetingbynaturalproducts
AT khanabdulq roleofnonreceptortyrosinekinasesinhematologicalmalignancesanditstargetingbynaturalproducts
AT merhimaysaloun roleofnonreceptortyrosinekinasesinhematologicalmalignancesanditstargetingbynaturalproducts
AT dermimesaid roleofnonreceptortyrosinekinasesinhematologicalmalignancesanditstargetingbynaturalproducts
AT uddinshahab roleofnonreceptortyrosinekinasesinhematologicalmalignancesanditstargetingbynaturalproducts