Cell signaling by receptor-tyrosine kinases

By M. Lemmon, Joseph Schlessinger. Cell, 2000

4,465 citations recorded by the source corpus.

Recent structural studies of receptor tyrosine kinases (RTKs) have revealed unexpected diversity in the mechanisms of their activation by growth factor ligands. Strategies for inducing dimerization by ligand binding are surprisingly diverse, as are mechanisms that couple this event to activation of the intracellular tyrosine kinase domains. As our understanding of these details becomes increasingly sophisticated, it provides an important context for therapeutically countering the effects of pathogenic RTK mutations in cancer and other diseases. Much remains to be learned, however, about the complex signaling networks downstream from RTKs and how alterations in these networks are translated into cellular responses.

Subfields: Molecular Biology, Oncology

View Paper: https://www.semanticscholar.org/paper/36ce235ced805b2fd761c18732c390558f98c424

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Molecular Biology

1. W. Chan
2. Tony Pawson
3. R. Roskoski
4. Ivan Dikic
5. Y. L. Deribe
6. M. Lemmon
7. D. Graham
8. Anica M Wandler

In Oncology

1. R. Roskoski
2. Tony Pawson
3. M. Lemmon
4. Ivan Dikic
5. D. Graham
6. Anica M Wandler
7. H. Earp
8. A. Keating

Citations in the corpus

• Fibroblast Growth Factors: Biology, Function, and Application for Tissue Regeneration (2010, background): “Signaling complexes are formed and recruited to the active receptors resulting in a cascade of phosphorylation events [20].”
• A Transgenic Drosophila Model Demonstrates That the Helicobacter pylori CagA Protein Functions as a Eukaryotic Gab Adaptor (2008, background): “Drosophila RTK signaling proteins are highly conserved with their mammalian orthologues and oncogenic mutations in these proteins, such as those that constitutively activate RTK receptors or their downstream effectors, function similarly in both Drosophila and mammalian cells [19].”
• TAM receptor tyrosine kinases: biologic functions, signaling, and potential therapeutic targeting in human cancer. (2008, background): “Typical activation of RTKs involves ligand binding to the extracellular domain (Schlessinger, 2000).”
• Insulin signaling in osteoblasts integrates bone remodeling and energy metabolism (2010, background): “Receptor tyrosine kinases are often inhibited by protein tyrosine phosphatases (PTPs) (Schlessinger, 2000) and PTP1B, which dephosphorylates the insulin receptor, is a major regulator of insulin signaling in hepatocytes and myocytes (Delibegovic et al.”
• A Comprehensive Review on MAPK: A Promising Therapeutic Target in Cancer (2019, background): “One such example consists of the epithelial growth factor (EGF), which targets its high-affinity membrane receptor (EGFR: epidermal growth factor receptor) [20].”