Related Experiment Video
Updated: Jul 13, 2026
07:42
Assessment of Resistance to Tyrosine Kinase Inhibitors by an Interrogation of Signal Transduction Pathways by Antibody Arrays
Published on: September 19, 2018
Structural analysis of receptor tyrosine kinases
1Skirball Institute of Biomolecular Medicine, New York University Medical Center, New York 10016, USA. hubbard@tallis.med.nyu.edu
Progress in Biophysics and Molecular Biology
|June 4, 1999
Summary
Receptor tyrosine kinases (RTKs) are crucial for cell signaling. Structural studies reveal how these proteins bind ligands and activate signaling pathways through dimerization and phosphorylation.
Area of Science:
- Molecular Biology
- Cell Signaling
- Structural Biology
Background:
- Receptor tyrosine kinases (RTKs) are transmembrane proteins central to cellular communication.
- They regulate critical processes like cell proliferation, differentiation, migration, and metabolism.
- Key examples include insulin and growth factor receptors (e.g., EGF, FGF, VEGF).
Purpose of the Study:
- To review recent structural studies on RTKs.
- To elucidate the molecular mechanisms of RTK ligand recognition and activation.
- To highlight advances in understanding RTK dimerization and autophosphorylation.
Main Methods:
- X-ray crystallography was employed to determine RTK structures.
- Analysis of structural data to understand ligand binding interfaces.
- Investigation of structural changes upon receptor dimerization and autophosphorylation.
Main Results:
- Structural insights into ligand-binding domains of various RTKs.
- Detailed mechanisms of receptor dimerization induced by ligand binding.
- Understanding the role of tyrosine autophosphorylation in signal transduction initiation.
- Identification of phosphotyrosine residues as docking sites for downstream effectors.
Conclusions:
- Structural biology has significantly advanced the understanding of RTK function.
- RTK activation involves precise conformational changes driven by ligand binding and dimerization.
- These findings provide a molecular basis for RTK-mediated signaling pathways.
Related Concept Videos
01:00Enzyme-linked Receptors
Enzyme-linked receptors are proteins that act as both receptor and enzyme, activating multiple intracellular signals. This is a large group of receptors that include the receptor tyrosine kinase (RTK) family. Many growth factors and hormones bind to and activate the RTKs.
Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...
Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...
01:00Enzyme-linked Receptors
Enzyme-linked receptors are proteins that act as both receptor and enzyme, activating multiple intracellular signals. This is a large group of receptors that include the receptor tyrosine kinase (RTK) family. Many growth factors and hormones bind to and activate the RTKs.
Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...
Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...
01:30Assembly of Signaling Complexes
Multiprotein signaling complexes are formed in a dynamic process involving protein-protein interactions at the cytoplasmic domain of transmembrane receptors or enzymatic and non-enzymatic proteins associated with the receptor. These complexes ensure the activation and propagation of intracellular signals that regulate cell functions.
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
01:22Amplifying Signals via Enzymatic Cascade
When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze the...
01:26Receptor Tyrosine Kinases
Receptor tyrosine kinases or RTKs are membrane-bound receptors that phosphorylate specific tyrosine on protein substrates. RTKs regulate cellular growth, differentiation, survival, and migration. They contain an extracellular ligand binding domain, a transmembrane domain, and a cytosolic tail with intrinsic kinase activity. Several extracellular signaling molecules activate RTKs in one or more ways and relay the signal downstream. Ligands such as platelet-derived growth factor (PDGF) or...
01:27Transducer Mechanism: Enzyme-Linked Receptors
Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:
Major types that are helpful drug targets include: