Abstract
Src homology 2 (SH2)-containing protein tyrosine phosphatase 2 (SHP2), encoded by the human PTPN11 gene, is a ubiquitously expressed protein tyrosine phosphatase (PTP) that consists of two tandem Src homology (SH2) domains (N-SH2 and C-SH2), a PTP catalytic domain, and a C-terminal tail with tyrosyl phosphorylation sites. It plays critical roles in numerous cellular processes through the regulation of various signaling pathways in PTP catalytic activity-dependent and -independent manners. Dysfunction of SHP2 resulting from pathogenic mutations and aberrant expression leads to the dysregulation of multiple signaling pathways, thus contributing to different human disorders. Germline and somatic mutations in PTPN11 are involved in Noonan syndrome (NS), LEOPARD syndrome (LS), and hematological malignancies, as well as several solid tumors. In this report, we provide an overview of the current knowledge of the structure and function of SHP2, and further discuss the molecular and pathogenic mechanism of SHP2 in human diseases, with a special focus on tumorigenesis. Furthermore, we summarize that SHP2 might itself represent a potential drug target for cancer prevention and treatment. Ongoing research and development of SHP2-specific inhibitors would enhance this potential.
Keywords: Hematologic malignancies, LEOPARD syndrome, Noonan syndromes, PTPN11, SHP2, tumorigenesis.
Current Cancer Drug Targets
Title:Structure, Function, and Pathogenesis of SHP2 in Developmental Disorders and Tumorigenesis
Volume: 14 Issue: 6
Author(s): Wen-Qing Huang, Qing Lin, Xuan Zhuang, Liang-Liang Cai, Run-Sheng Ruan, Zhong-Xian Lu and Chi-Meng Tzeng
Affiliation:
Keywords: Hematologic malignancies, LEOPARD syndrome, Noonan syndromes, PTPN11, SHP2, tumorigenesis.
Abstract: Src homology 2 (SH2)-containing protein tyrosine phosphatase 2 (SHP2), encoded by the human PTPN11 gene, is a ubiquitously expressed protein tyrosine phosphatase (PTP) that consists of two tandem Src homology (SH2) domains (N-SH2 and C-SH2), a PTP catalytic domain, and a C-terminal tail with tyrosyl phosphorylation sites. It plays critical roles in numerous cellular processes through the regulation of various signaling pathways in PTP catalytic activity-dependent and -independent manners. Dysfunction of SHP2 resulting from pathogenic mutations and aberrant expression leads to the dysregulation of multiple signaling pathways, thus contributing to different human disorders. Germline and somatic mutations in PTPN11 are involved in Noonan syndrome (NS), LEOPARD syndrome (LS), and hematological malignancies, as well as several solid tumors. In this report, we provide an overview of the current knowledge of the structure and function of SHP2, and further discuss the molecular and pathogenic mechanism of SHP2 in human diseases, with a special focus on tumorigenesis. Furthermore, we summarize that SHP2 might itself represent a potential drug target for cancer prevention and treatment. Ongoing research and development of SHP2-specific inhibitors would enhance this potential.
Export Options
About this article
Cite this article as:
Huang Wen-Qing, Lin Qing, Zhuang Xuan, Cai Liang-Liang, Ruan Run-Sheng, Lu Zhong-Xian and Tzeng Chi-Meng, Structure, Function, and Pathogenesis of SHP2 in Developmental Disorders and Tumorigenesis, Current Cancer Drug Targets 2014; 14 (6) . https://dx.doi.org/10.2174/1568009614666140717105001
DOI https://dx.doi.org/10.2174/1568009614666140717105001 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
Call for Papers in Thematic Issues
Advances in Cancer Biomarkers and Potential Drug Targets: From Diagnosis to Therapy
Cancer biomarkers play a crucial role in the diagnosis, prognosis, and treatment of cancer. They provide valuable information for cancer detection, risk assessment, treatment selection, and monitoring response to therapy. With advancements in molecular biology and high-throughput technologies, there has been an increasing interest in identifying and characterizing cancer biomarkers ...read more
Novel Therapeutic Approaches to Target Drug Resistant Tumors
With the development of disciplines such as chemical biology and molecular biology, the genes or proteins closely related to tumor occurrence and development have gradually become clear. Targeted therapies targeting these genes or proteins provide more effective methods for tumor treatment. Tumor targeted drugs generally only act on specific targets ...read more
ROLE OF IMMUNE AND GENOTOXIC RESPONSE BIOMARKERS IN TUMOR MICROENVIRONMENT IN CANCER DIAGNOSIS AND TREATMENT
Biological biomarkers have been used in medical research as an indicator of a normal or abnormal process inside the body, or of a disease. Nowadays, various researchers are in process to explore and investigate the biological markers for the early assessment of cancer. DNA Damage response (DDR) pathways and immune ...read more
Targeting the battlefield between host and tumor: basic research and clinical practice on reshaping tumor immune microenvironment
Immune system protects host against malignant tumors through effector cells and molecules. Cancer development and its response to therapy are regulated by inflammation, which either promotes or suppresses cancer progression. Chronic inflammation facilitates cancer progression and treatment resistance, whereas induction of acute inflammatory reactions often lead to anti-cancer immune responses. ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Pandemic Influenza: Preventing the Emergence of Novel Strains and Countermeasures to Ameliorate its Effects
Infectious Disorders - Drug Targets The Future of Induced Pluripotent Stem Cells for Cardiac Therapy and Drug Development
Current Pharmaceutical Design Crosstalk Between Bioactive Peptide and Intestinal Barrier in Gut Homeostasis
Current Protein & Peptide Science Antimicrobial Peptides Present in Mammalian Skin and Gut are Multifunctional Defence Molecules
Current Pharmaceutical Design Feline Immunodeficiency Virus Model for Designing HIV/AIDS Vaccines
Current HIV Research Role of Tyrosine Phosphatase Inhibitors in Cancer Treatment with Emphasis on SH2 Domain-Containing Tyrosine Phosphatases (SHPs)
Anti-Cancer Agents in Medicinal Chemistry Human Induced Pluripotent Stem Cells for Inherited Cardiovascular Diseases Modeling
Current Stem Cell Research & Therapy The Role of SHP-2 in Cell Signalling and Human Disease
Current Enzyme Inhibition Induced Pluripotent Stem Cells and Their Potential for Basic and Clinical Sciences
Current Cardiology Reviews Previously Apparently Undescribed Autosomal-Recessive Multiple Congenital Anomalies/ Mental Retardation (MCA/MR) Syndrome Comprising: Fronto-Nasal Dysplasia, Hypertelorism, Short Stature and Brachydactily
Current Pediatric Reviews Induced Pluripotent Stem Cell Technology: A Paradigm Shift in Medical Science for Drug Screening and Disease Modeling
Current Medicinal Chemistry Tissue Engineering Techniques in Cardiac Repair and Disease Modelling
Current Pharmaceutical Design Evasion of Ribonuclease Inhibitor as a Determinant of Ribonuclease Cytotoxicity
Current Pharmaceutical Biotechnology Beta-Blockers in Pediatric Hypertrophic Cardiomyopathies
Reviews on Recent Clinical Trials SHP-2 Regulates Growth Factor Dependent Vascular Signalling and Function
Mini-Reviews in Medicinal Chemistry Antibodies for Therapeutic Uses and the Evolution of Biotechniques
Current Medicinal Chemistry Phosphotyrosine Phosphatases in Cancer Diagnostic and Treatment
Recent Patents on DNA & Gene Sequences Enzymatic Properties and Physiological Roles of Cytosolic 5’-Nucleotidase II.
Current Medicinal Chemistry Induced Pluripotent Stem Cell-Based Studies of Parkinson's Disease: Challenges and Promises
CNS & Neurological Disorders - Drug Targets Antimicrobial Peptides in Oral Cancer
Current Pharmaceutical Design