Abstract
CD45 is expressed on all nucleated haematopoietic cells and was originally identified as the first and prototypic transmembrane protein tyrosine phosphatase (PTPase). CD45 has been extensively studied for over two decades as a PTPase that functions in antigen receptor signaling by dephosphorylation of Srckinases. CD45 can operate as a positive as well negative regulator of Src-family kinases. In CD45 mutant cell lines, CD45-deficient mice, and CD45-deficient human SCID patients, CD45 is required for signal transduction through antigen receptors. Our group has recently shown that CD45 can also function as a Janus kinase (JAK) tyrosine phosphatase that negatively regulates cytokine receptor signaling involved in the differentiation, proliferation, and antiviral immunity of haematopoietic cells. Moreover, a point mutation in CD45, implicated in affecting CD45 dimerization, and a genetic polymorphism that affects alternative CD45 splicing have been implicated in autoimmunity in mice and humans. CD45 is expressed in multiple isoforms and modulation of specific CD45 splice variants with antibodies can prevent transplant rejections. Moreover, loss of CD45 can affect microglia activation in a mouse model for Alzheimers disease. Modulation of CD45 splice variants and CD45 activity might provide a unique opportunity to design drugs that turn off or turn-on antigen and cytokine receptor signaling in cancer, allergy, transplantation, or autoimmunity.
Keywords: CD45 Regulated Signaling, haematopoietic cells, Srckinases, autoimmunity, mutant cell
Current Topics in Medicinal Chemistry
Title: CD45 Regulated Signaling Pathways
Volume: 3 Issue: 7
Author(s): Junko Irie-Sasaki, Takehiko Sasaki and Josef M. Penninger
Affiliation:
Keywords: CD45 Regulated Signaling, haematopoietic cells, Srckinases, autoimmunity, mutant cell
Abstract: CD45 is expressed on all nucleated haematopoietic cells and was originally identified as the first and prototypic transmembrane protein tyrosine phosphatase (PTPase). CD45 has been extensively studied for over two decades as a PTPase that functions in antigen receptor signaling by dephosphorylation of Srckinases. CD45 can operate as a positive as well negative regulator of Src-family kinases. In CD45 mutant cell lines, CD45-deficient mice, and CD45-deficient human SCID patients, CD45 is required for signal transduction through antigen receptors. Our group has recently shown that CD45 can also function as a Janus kinase (JAK) tyrosine phosphatase that negatively regulates cytokine receptor signaling involved in the differentiation, proliferation, and antiviral immunity of haematopoietic cells. Moreover, a point mutation in CD45, implicated in affecting CD45 dimerization, and a genetic polymorphism that affects alternative CD45 splicing have been implicated in autoimmunity in mice and humans. CD45 is expressed in multiple isoforms and modulation of specific CD45 splice variants with antibodies can prevent transplant rejections. Moreover, loss of CD45 can affect microglia activation in a mouse model for Alzheimers disease. Modulation of CD45 splice variants and CD45 activity might provide a unique opportunity to design drugs that turn off or turn-on antigen and cytokine receptor signaling in cancer, allergy, transplantation, or autoimmunity.
Export Options
About this article
Cite this article as:
Irie-Sasaki Junko, Sasaki Takehiko and Penninger M. Josef, CD45 Regulated Signaling Pathways, Current Topics in Medicinal Chemistry 2003; 3 (7) . https://dx.doi.org/10.2174/1568026033452339
DOI https://dx.doi.org/10.2174/1568026033452339 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
Adaptogens—History and Future Perspectives
Adaptogens are pharmacologically active compounds or plant extracts that are associated with the ability to enhance the body’s stability against stress. The intake of adaptogens is associated not only with a better ability to adapt to stress and maintain or normalise metabolic functions but also with better mental and physical ...read more
AlphaFold in Medicinal Chemistry: Opportunities and Challenges
AlphaFold, a groundbreaking AI tool for protein structure prediction, is revolutionizing drug discovery. Its near-atomic accuracy unlocks new avenues for designing targeted drugs and performing efficient virtual screening. However, AlphaFold's static predictions lack the dynamic nature of proteins, crucial for understanding drug action. This is especially true for multi-domain proteins, ...read more
Artificial intelligence for Natural Products Discovery and Development
Our approach involves using computational methods to predict the potential therapeutic benefits of natural products by considering factors such as drug structure, targets, and interactions. We also employ multitarget analysis to understand the role of drug targets in disease pathways. We advocate for the use of artificial intelligence in predicting ...read more
Chemistry Based on Natural Products for Therapeutic Purposes
The development of new pharmaceuticals for a wide range of medical conditions has long relied on the identification of promising natural products (NPs). There are over sixty percent of cancer, infectious illness, and CNS disease medications that include an NP pharmacophore, according to the Food and Drug Administration. Since NP ...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
- Announcements
Related Articles
-
Clinical Evaluation of the Effect of Blueberries Consumption on Chronic Diseases, Illness Prevention and Health Promotion
The Natural Products Journal Knowing is Half the Battle: Targeting Virulence Factors of Group A Streptococcus for Vaccine and Therapeutics
Current Drug Targets Oxidative Status in Multiple Sclerosis and Off-Targets of Antioxidants: The Case of Edaravone
Current Medicinal Chemistry Does Human Alpha-Synuclein Behave Like Prions?
CNS & Neurological Disorders - Drug Targets Vitamin A and Diabesity: New Insight for Drug Discovery
Mini-Reviews in Medicinal Chemistry Functional Protein Analysis Using Mass Spectrometry
Current Organic Chemistry IL-1 Cytokines in Cardiovascular Disease: Diagnostic, Prognostic and Therapeutic Implications
Cardiovascular & Hematological Agents in Medicinal Chemistry Editorial [Hot Topic: Drugs Targeting Atherosclerosis: Current and Emerging Approaches (Executive Editors: Vangelis G. Manolopoulos and Anna Tavridou)]
Current Pharmaceutical Design Association Between Anemia and Dementia: A Nationwide, Populationbased Cohort Study in Taiwan
Current Alzheimer Research Ultrasound Contrast Agents: Updated Data on Safety Profile
Current Pharmaceutical Design Current Advances in the Treatment of Parkinsons Disease with Stem Cells
Current Neurovascular Research The Antioxidants and Pro-Antioxidants Network: An Overview
Current Pharmaceutical Design Blood Serum Atherogenicity: Cellular Test for the Development of Anti- Atherosclerotic Therapy
Current Pharmaceutical Design Statins Attenuate Fibrotic Manifestations of Cardiac Tissue Damage
Current Molecular Pharmacology Strategies for Integral Metabolism Profile of Multiple Compounds in Herbal Medicines: Pharmacokinetics, Metabolites Characterization and Metabolic Interactions
Current Drug Metabolism Myocardial Infarction with Non Obstructive Coronary Atherosclerosis: A Case Report
New Emirates Medical Journal T Cell Replicative Senescence in Human Aging
Current Pharmaceutical Design Phytoestrogens and Mitochondrial Biogenesis in Breast Cancer. Influence of Estrogen Receptors Ratio
Current Pharmaceutical Design Utilization of Evidence-Based Secondary Prevention Medications at the Time of Discharge in Patients with Acute Coronary Syndrome (ACS) in Qatar
Current Vascular Pharmacology Type 2 Diabetes Mellitus and the Elderly: An Update on Drugs Used to Treat Glycaemia
Current Vascular Pharmacology