Abstract
The reversible phosphorylation of tyrosine residues in proteins, which is governed by the balanced action of protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs), is a key element of the signaling pathways that are involved in the control of cell proliferation. Deregulation of either of these key regulators leads to abnormal cell signaling, which is largely associated with human pathologies including cancer. This review focuses on recent studies on the role of the protein tyrosine phosphatase SHP-1 on cell-cycle regulation and its possible roles in tumour onset and progression. SHP-1 is a PTP with two SH2 domains that is expressed in haematopoietic cells and, moderately, in many other cell types, especially malignant epithelial cells. SHP-1 regulates cell proliferation, whether it is by controlling mitogenic pathways activated by receptors with tyrosine kinase activity, or by regulating components of the cell-cycle machinery such as CDK2, p27 and cyclin D1. Since several inhibitors targeting SHP-1 have demonstrated their value in cancer treatment, this phosphatase has been proposed as a therapeutic target for this pathology.
Keywords: Protein tyrosine phosphatase, p27, CDK2, cyclin D, SH2 domain, cancer, PTPN6, PTKs, pRb, TCR, cGMP
Anti-Cancer Agents in Medicinal Chemistry
Title: SHP-1 in Cell-Cycle Regulation
Volume: 11 Issue: 1
Author(s): Pilar Lopez-Ruiz, Javier Rodriguez-Ubreva, Ariel Ernesto Cariaga, Maria Alicia Cortes and Begona Colas
Affiliation:
Keywords: Protein tyrosine phosphatase, p27, CDK2, cyclin D, SH2 domain, cancer, PTPN6, PTKs, pRb, TCR, cGMP
Abstract: The reversible phosphorylation of tyrosine residues in proteins, which is governed by the balanced action of protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs), is a key element of the signaling pathways that are involved in the control of cell proliferation. Deregulation of either of these key regulators leads to abnormal cell signaling, which is largely associated with human pathologies including cancer. This review focuses on recent studies on the role of the protein tyrosine phosphatase SHP-1 on cell-cycle regulation and its possible roles in tumour onset and progression. SHP-1 is a PTP with two SH2 domains that is expressed in haematopoietic cells and, moderately, in many other cell types, especially malignant epithelial cells. SHP-1 regulates cell proliferation, whether it is by controlling mitogenic pathways activated by receptors with tyrosine kinase activity, or by regulating components of the cell-cycle machinery such as CDK2, p27 and cyclin D1. Since several inhibitors targeting SHP-1 have demonstrated their value in cancer treatment, this phosphatase has been proposed as a therapeutic target for this pathology.
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Lopez-Ruiz Pilar, Rodriguez-Ubreva Javier, Ernesto Cariaga Ariel, Alicia Cortes Maria and Colas Begona, SHP-1 in Cell-Cycle Regulation, Anti-Cancer Agents in Medicinal Chemistry 2011; 11 (1) . https://dx.doi.org/10.2174/187152011794941154
DOI https://dx.doi.org/10.2174/187152011794941154 |
Print ISSN 1871-5206 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5992 |
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