# Lemmon and Schlessinger 2010: cell signalling by receptor tyrosine kinases

Source: https://onco.cc/key-papers/paper-lemmon-schlessinger-rtk-signalling-cell-2010/  
OnCo record `paper-lemmon-schlessinger-rtk-signalling-cell-2010` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

The standard review of the receptor family behind many cancer drugs, explaining how growth factor receptors such as EGFR and HER2 switch on when they pair up, how mutations lock them on in cancer, and how inhibitors turn them off.

## Summary

Lemmon and Schlessinger surveyed the 58 human receptor tyrosine kinases in 20 subfamilies, describing how ligand binding drives receptor dimerisation and trans-autophosphorylation, the structural diversity of activation mechanisms across families, and the intracellular pathways (RAS-MAPK, PI3K-AKT, PLC-gamma and STAT) that carry the signal. They explained how overexpression, amplification, point mutations and fusions deregulate these receptors in cancer and how antibodies and small-molecule kinase inhibitors exploit the same mechanisms, with resistance mutations as the predictable consequence.

## Fields

- Kind: Key paper
- Last checked: 2026-09-08
- Journal: Cell
- Year: 2010
- DOI: 10.1016/j.cell.2010.06.011
- Authors: Lemmon MA, Schlessinger J.
- Findings: Humans have 58 receptor tyrosine kinases in 20 subfamilies, activated by ligand-induced dimerisation and trans-autophosphorylation with family-specific mechanisms.; Signals propagate through RAS-MAPK, PI3K-AKT, PLC-gamma and STAT pathways and are shaped by negative feedback and endocytosis.; Cancers deregulate RTKs by amplification, mutation and fusion; therapeutic antibodies and kinase inhibitors target the receptors and select for resistance mutations.
- What it means: Almost every targeted therapy on this site, from trastuzumab and EGFR inhibitors to ALK, MET, RET and FGFR drugs, acts on the receptors this review describes. It is the mechanistic background for understanding both why these drugs work and why resistance mutations arise.
- Caveats: A review; structural details for several families have been refined since.; Does not cover the clinical trials of the drugs it explains.

## Sources

- Full text (DOI): https://doi.org/10.1016/j.cell.2010.06.011

## Connected records

- targets: [ALK](https://onco.cc/targets/alk/), [EGFR](https://onco.cc/targets/egfr/), [HER2](https://onco.cc/targets/her2/), [KIT](https://onco.cc/targets/kit/), [MET](https://onco.cc/targets/met/)
- pathways: [Receptor tyrosine kinase activation](https://onco.cc/pathways/rtk-activation/)
- terms: [Signalling pathway](https://onco.cc/terms/signalling-pathway/), [Tyrosine kinase inhibitor (TKI)](https://onco.cc/terms/tki-term/)
- key papers: [Yarden and Sliwkowski 2001: untangling the ErbB signalling network](https://onco.cc/key-papers/paper-yarden-sliwkowski-erbb-network-nrmcb-2001/)

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