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Focus on dimerization

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Structure of a dimerized receptor complex

This image shows the crystal structure of the extracellular portion of a dimerized pair of HER1/EGFR receptors. Note that the 2 receptors are bound to each other as well as to 2 molecules of EGF, a ligand specific to HER1/EGFR. Dimerization enables activation of the tyrosine kinase domain of the receptors and subsequent molecular signaling within the cell.^1,3 Reprinted from Cell vol 110, Ogiso H, Ishitani R, Nureki O, et al. Crystal structure of the complex of human epidermal growth factor and receptor extracellular domains, pp 775-787, Copyright 2002, with permission from Elsevier.

Dimerization is a key step in HER signaling pathways

Activation of HER family receptors does not occur until the receptors have dimerized, making dimerization a critical step in the cellular signaling process³

HER receptor dimers have multiple effects on cellular signaling

With 4 members of the HER family of receptors, each of which is able to homodimerize or to heterodimerize with other members of the HER family, multiple receptor combinations are possible.¹

Each possible pairing of HER family receptors stimulates a different combination of signaling pathways within the cell¹
- These pathways overlap, creating a highly complex system of signals
HER2 is the preferred dimerization partner for all members of the HER family of receptors^1,7
- However, less common dimers not including HER2, such as the HER3/HER4 heterodimer, do exist⁵
Signals from dimerized, activated HER family receptors can lead to multiple effects, including^1,5:
- Growth
- Proliferation
- Survival/decreased apoptosis
- Cellular migration
- Angiogenesis

Next Section: HER signaling pathways influence many types of cancer

References

Research HER Pathways

Overview