Abstract
Signal transducer and activator of transcription (STAT) proteins are second messengers in the JAK/STAT signaling pathway. The activation mechanism of STAT proteins involves phosphorylation on a single tyrosine residue by Janus-activated family kinases (JAK) in response to the binding of a series of extracellular proteins, such as cytokines, growth factors, hormones and membrane receptors. Activated via phosphorylation, STATs dissociate from the receptor, undergo dimerization and translocate to the nucleus, where they induce the transcription of target genes, commonly referred to as Interferon stimulated genes (ISGs). The family of STAT proteins has been documented to participate in normal cellular events, such as differentiation, proliferation, cell survival, apoptosis and angiogenesis. Constitutively activated STATs are involved in an aberrant signaling pathway which has transforming properties and occurs in cancer development. This review describes the mechanisms of JAK/STAT activation in normal and cancer cells. Moreover, it outlines the role of the JAK/STAT pathway in the inflammatory process as well as in oncogenesis. Additionally, the contribution of STAT and JAK proteins in molecular targeted cancer therapy is discussed.
Keywords: STAT proteins, JAK/STAT signaling pathway, inflammation, targeted therapy, cancer development, dimerization, phosphorylation, oligomerization, β-isoform, docking site
Current Signal Transduction Therapy
Title:Review: The JAK/STAT Protein Activation – Role in Cancer Development and Targeted Therapy
Volume: 7 Issue: 3
Author(s): Daria Domanska and Ewa Brzezianska
Affiliation:
Keywords: STAT proteins, JAK/STAT signaling pathway, inflammation, targeted therapy, cancer development, dimerization, phosphorylation, oligomerization, β-isoform, docking site
Abstract: Signal transducer and activator of transcription (STAT) proteins are second messengers in the JAK/STAT signaling pathway. The activation mechanism of STAT proteins involves phosphorylation on a single tyrosine residue by Janus-activated family kinases (JAK) in response to the binding of a series of extracellular proteins, such as cytokines, growth factors, hormones and membrane receptors. Activated via phosphorylation, STATs dissociate from the receptor, undergo dimerization and translocate to the nucleus, where they induce the transcription of target genes, commonly referred to as Interferon stimulated genes (ISGs). The family of STAT proteins has been documented to participate in normal cellular events, such as differentiation, proliferation, cell survival, apoptosis and angiogenesis. Constitutively activated STATs are involved in an aberrant signaling pathway which has transforming properties and occurs in cancer development. This review describes the mechanisms of JAK/STAT activation in normal and cancer cells. Moreover, it outlines the role of the JAK/STAT pathway in the inflammatory process as well as in oncogenesis. Additionally, the contribution of STAT and JAK proteins in molecular targeted cancer therapy is discussed.
Export Options
About this article
Cite this article as:
Domanska Daria and Brzezianska Ewa, Review: The JAK/STAT Protein Activation – Role in Cancer Development and Targeted Therapy, Current Signal Transduction Therapy 2012; 7 (3) . https://dx.doi.org/10.2174/157436212802481619
DOI https://dx.doi.org/10.2174/157436212802481619 |
Print ISSN 1574-3624 |
Publisher Name Bentham Science Publisher |
Online ISSN 2212-389X |
- 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
- Announcements
Related Articles
-
Regulation of the Endoplasmic Reticulum Ca2+-Store in Cancer
Anti-Cancer Agents in Medicinal Chemistry Crosstalk Between Epidermal Growth Factor Receptor- and Insulin-Like Growth Factor-1 Receptor Signaling: Implications for Cancer Therapy
Current Cancer Drug Targets Drug-Eluting Stents: Present and Future
Cardiovascular & Hematological Agents in Medicinal Chemistry The miRNAs and Epithelial-Mesenchymal Transition in Cancers
Current Pharmaceutical Design Assessment of the Health Effects of Chemicals in Humans: II. Construction of an Adverse Effects Database for QSAR Modeling
Current Drug Discovery Technologies Fentanyl for Breakthrough Cancer Pain: Where are We?
Reviews on Recent Clinical Trials Protective Mechanisms of Helminths Against Reactive Oxygen Species are Highly Promising Drug Targets
Current Medicinal Chemistry RECKing MMP: Relevance of Reversion-inducing Cysteine-rich Protein with Kazal Motifs as a Prognostic Marker and Therapeutic Target for Cancer (A Review)
Anti-Cancer Agents in Medicinal Chemistry Functional Food with Some Health Benefits, So Called Superfood: A Review
Current Nutrition & Food Science The Interactions Between Diabetes Mellitus and Myelodysplastic Syndromes: Current State of Evidence and Future Directions
Current Diabetes Reviews Role of Radiopharmaceuticals in Development of Inhaled Drugs
Current Pharmaceutical Design Thyroid Ultrasound and Other Imaging Procedures in the Pediatric Age
Current Pediatric Reviews Diabetes Mellitus as a Risk Factor for Cancer: Stress or Viral Etiology?
Infectious Disorders - Drug Targets Mast Cells in Lung Homeostasis: Beyond Type I Hypersensitivity
Current Respiratory Medicine Reviews Anti-IL-13 in Inflammatory Bowel Disease: From the Bench to the Bedside
Current Drug Targets Chondroitin Sulfate and Sulfur Containing Chondroprotective Agents: Is there a Basis for their Pharmacological Action?
Current Rheumatology Reviews Development of Natural Bioactive Alkaloids: Anticancer Perspective
Mini-Reviews in Medicinal Chemistry An Update of Radiolabeled Bombesin Analogs for Gastrin-Releasing Peptide Receptor Targeting
Current Pharmaceutical Design Hydrogen Sulfide Generation in Mammals: The Molecular Biology of Cystathionine-β-Synthase (CBS) and Cystathionine-γ-Lyase (CSE)
Inflammation & Allergy - Drug Targets (Discontinued) subject Index To Volume 3
Current Drug Targets