What is the Difference Between EGFR and HER2

The key difference between EGFR and HER2 is that EGFR is a receptor of the ErbB family that activates directly through binding to its ligand, while HER2 is a receptor of the ErbB family that activates from heterodimerization with another ErbB member or by homodimerization when HER2 concentrations are high.

The ErbB family of receptors are proteins. This family contains four receptor tyrosine kinases. These proteins are structurally related. The epidermal growth factor receptor (EGFR) is the first discovered member in this family. In humans, this family includes EGFR (ErbB1), Her2 (ErbB2), Her3 (ErbB3), and Her4 (ErbB4).

CONTENTS

1. Overview and Key Difference
2. What is EGFR  
3. What is HER2
4. Similarities –  EGFR and HER2
5. EGFR vs. HER2 in Tabular Form
6. Summary – EGFR vs HER2

What is EGFR?

Epidermal growth factor receptor (EGFR) is a transmembrane protein that works as a receptor. It is also known as ErbB-1 or HER1 in humans. It acts as a receptor for extracellular protein ligands, which are members of the epidermal growth factor family (EGF family). These receptors are a member of the ErbB family of receptors. Stanley Cohen of Vanderbilt University discovered this.

Moreover, EGFR is activated by binding of its specific ligands, such as epidermal growth factor and transforming growth factor alpha (TGF-α). Upon activation, it undergoes a transition from an inactive monomeric form to an active homodimer form. Furthermore, there is evidence that EGFR may pair with another member of the ErbB receptor family, like ErbB2 or Her2. This creates an activated heterodimer. EGFR dimerization triggers its intrinsic intracellular protein tyrosine kinase activity, and this causes the autophosphorylation of several tyrosine residues in the C-terminal domain of the EGFR molecule. Furthermore, this autophosphorylation elicits downstream signaling by several other proteins and several signal transduction cascades, such as MAPK, Akt, and JNK pathways. These pathways ultimately lead to DNA synthesis and cell proliferation. Deficient signaling of EGFR in humans is associated with diseases such as Alzheimer’s, whereas over-expression is associated with cancer development.

What is HER2?

HER2 is a member of the ErbB receptor family that becomes activated through heterodimerization with another ErbB member, such as EGFR. This dimerization results in the autophosphorylation of tyrosine residues within the cytoplasmic domain of the HER2 receptor and initiates a variety of important signaling pathways in the cell. HER2 is the second member of this ERBB family of receptors.

In humans, the HER2 receptor is encoded by the ErbB2 gene. The ErbB2 gene is a proto-oncogene located at the long arm of human chromosome 17. Amplification or over-expression of HER2 is involved in the development and progression of certain aggressive types of breast cancer. Recently, HER2 has emerged as a significant biomarker and therapeutic target for approximately 30% of breast cancers in women.

What are the Similarities Between EGFR and HER2?

• EGFR and HER2 are two members of the ErbB family of receptors.
• Both are transmembrane receptors.
• Both receptors contain an extracellular ligand binding domain, a transmembrane domain, and an intracellular domain.
• They stimulate downstream signaling pathways.
• Defects in their expressions cause different diseases in humans.

What is the Difference Between EGFR and HER2?

EGFR is a receptor of the ErbB family that activates directly through binding to its ligand, while HER2 is a receptor of the ErbB family that activates from heterodimerization with another ErbB member or by homodimerization when HER2 concentrations are high. Thus, this is the key difference between EGFR and HER2. Furthermore, the EGFR receptor is encoded by the EGFR gene located in chromosome 7, while the HER2 receptor is encoded by the ErbB2 gene located in chromosome 17.

The infographic below presents the differences between EGFR and HER2 in tabular form for side-by-side comparison.

Summary – EGFR vs HER2

The ErbB family of receptors has several receptors, including EGFR (ErbB1), Her2 (ErbB2), Her3 (ErbB3), and Her4 (ErbB4). Insufficient ErbB family receptors are associated with the development of neurodegenerative diseases like multiple sclerosis and Alzheimer’s disease in humans, whereas excessive ErbB family receptor signaling is associated with cancer development in humans. EGFR is a transmembrane receptor of the ErbB family that activates directly through binding to its ligand, such as TGF-α while HER2 is a transmembrane receptor of the ErbB family, that activates from heterodimerization with another ERBB member, such as EGFR. So, this summarizes the difference between EGFR and HER2.

Reference:

1. “Epidermal Growth Factor Receptor – An Overview.” ScienceDirect Topics.
2. “HER2.” StatPearls – NCBI Bookshelf.

Image Courtesy:

1. “126-EpidermalGrowthFactor EGFR” By David Goodsell – RCSB PDB Molecule of the Month (CC BY 3.0) via Commons Wikimedia
2. “Trastuzumab-HER2 complex 1N8Z” By Takuma-sa – Own work (CC0) via Commons Wikimedia