Abstract
This review summarises some of the knowledge we have about Crk and Grb2 family adaptor protein signalling in health and disease and outlines the current status and the challenges still remaining in the development of efficient and selective inhibitors of their protein - protein interactions. It also highlights briefly some recent successes and problems of inhibitors for proteins that functionally interact with Crk and Grb2 family adaptors, as well as opportunities, which may arise from combination therapies. Grb2 and Crk family adaptors regulate signalling pathways linked to human diseases. They are mainly composed of Src homology 2 (SH2) and Src homology 3 (SH3) domains, which serve as docking sites for signalling proteins, including various receptors, cytoplasmic kinases and GTPase regulators. Considerable insight into the biological functions and mechanisms of action of small SH2/SH3 domain adaptors has been gained in the last years from experimental approaches as diverse as targeted gene disruption and structural studies at the atomic level. This has already indicated several strategies to utilise SH2 and SH3 domain interaction inhibitors in human disease therapy. Additional molecular targets for Crk and Grb2 domain interaction blockers are expected to surface as further protein-protein interactions are discovered. Examples include newly found DOCK family proteins (DOCK3, DOCK4, and DOCK5) which are known or suspected effectors of Crk proteins and the interaction of Grb2 with the cell cycle regulator p27Kip1.
Keywords: Adaptor proteins, cancer, cell signalling, Crk, Grb2, Mona/Gads, inhibitor development
Current Pharmaceutical Design
Title: Potential Disease Targets for Drugs that Disrupt Protein - Protein Interactions of Grb2 and Crk Family Adaptors
Volume: 12 Issue: 5
Author(s): Stephan M. Feller and Marc Lewitzky
Affiliation:
Keywords: Adaptor proteins, cancer, cell signalling, Crk, Grb2, Mona/Gads, inhibitor development
Abstract: This review summarises some of the knowledge we have about Crk and Grb2 family adaptor protein signalling in health and disease and outlines the current status and the challenges still remaining in the development of efficient and selective inhibitors of their protein - protein interactions. It also highlights briefly some recent successes and problems of inhibitors for proteins that functionally interact with Crk and Grb2 family adaptors, as well as opportunities, which may arise from combination therapies. Grb2 and Crk family adaptors regulate signalling pathways linked to human diseases. They are mainly composed of Src homology 2 (SH2) and Src homology 3 (SH3) domains, which serve as docking sites for signalling proteins, including various receptors, cytoplasmic kinases and GTPase regulators. Considerable insight into the biological functions and mechanisms of action of small SH2/SH3 domain adaptors has been gained in the last years from experimental approaches as diverse as targeted gene disruption and structural studies at the atomic level. This has already indicated several strategies to utilise SH2 and SH3 domain interaction inhibitors in human disease therapy. Additional molecular targets for Crk and Grb2 domain interaction blockers are expected to surface as further protein-protein interactions are discovered. Examples include newly found DOCK family proteins (DOCK3, DOCK4, and DOCK5) which are known or suspected effectors of Crk proteins and the interaction of Grb2 with the cell cycle regulator p27Kip1.
Export Options
About this article
Cite this article as:
Feller M. Stephan and Lewitzky Marc, Potential Disease Targets for Drugs that Disrupt Protein - Protein Interactions of Grb2 and Crk Family Adaptors, Current Pharmaceutical Design 2006; 12 (5) . https://dx.doi.org/10.2174/138161206775474369
DOI https://dx.doi.org/10.2174/138161206775474369 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...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
-
Recent Patents and Patent Applications Relating to mTOR Pathway
Recent Patents on DNA & Gene Sequences pH-Sensitive PEGylated Liposomes Functionalized With a Fibronectin-Mimetic Peptide Show Enhanced Intracellular Delivery to Colon Cancer Cells
Current Pharmaceutical Biotechnology Tipping the Balance Between Life and Death: Targeting Histone Acetylation for Cancer Therapy
Drug Delivery Letters Meet Our Editorial Board Member:
Protein & Peptide Letters CDK Inhibitors Induce Mitochondria-mediated Apoptosis Through the Activation of Polyamine Catabolic Pathway in LNCaP, DU145 and PC3 Prostate Cancer Cells
Current Pharmaceutical Design Interaction of ABC Multidrug Transporters with Anticancer Protein Kinase Inhibitors: Substrates and/or Inhibitors?
Current Cancer Drug Targets Anionic Host Defence Peptides from the Plant Kingdom: Their Anticancer Activity and Mechanisms of Action
Protein & Peptide Letters Cancer and Phase II Drug-Metabolizing Enzymes
Current Drug Metabolism Power from the Garden: Plant Compounds as Inhibitors of the Hallmarks of Cancer
Current Medicinal Chemistry Retinoids in Clinical Use
Medicinal Chemistry Collateral Damage Control in Cancer Therapy: Defining the Stem Identity in Gliomas
Current Pharmaceutical Design Targeting Kinases in Cancer Therapies: Adverse Effects on Blood Platelets
Current Pharmaceutical Design Annexin A5 Imaging: An Academic Research – Clinical Trials and Theses
Current Molecular Imaging (Discontinued) Optimization of Lentiviral Vectors Generation for Biomedical and Clinical Research Purposes: Contemporary Trends in Technology Development and Applications
Current Gene Therapy Interferon-Beta Therapy Monitoring in Multiple Sclerosis Patients
Endocrine, Metabolic & Immune Disorders - Drug Targets Bugs as Drugs: Understanding the Linkage between Gut Microbiota and Cancer Treatment
Current Drug Targets The Use of Temozolomide for the Treatment of Malignant Tumors: Clinical Evidence and Molecular Mechanisms of Action
Recent Patents on Anti-Cancer Drug Discovery Insights into a Critical Role of the FOXO3a-FOXM1 Axis in DNA Damage Response and Genotoxic Drug Resistance
Current Drug Targets Annexins in the Central Nervous System: Are they Neuroprotective or Proapoptotic Agents?
Medicinal Chemistry Reviews - Online (Discontinued) The Phosphoinositide 3-Kinase (PI3K)/AKT Signaling Pathway as a Therapeutic Target for the Treatment of Human Acute Myeloid Leukemia (AML)
Current Signal Transduction Therapy