What Is the Function of the HER2 Protein in the Body?

Human Epidermal Growth Factor Receptor 2, commonly known as HER2, is a protein that has a significant function in human biology. It participates in the regulation of cell growth, survival, and differentiation. Its presence and activity levels are important for understanding how cells behave under normal physiological conditions.

When the systems that control HER2’s function are disrupted, it can lead to abnormal cellular processes. This dysregulation is particularly noted in specific types of cancer where the protein’s activity is amplified, making the study of HER2 relevant to both cellular biology and clinical science.

The HER2 Gene and Protein

The HER2 protein is produced from instructions in the ERBB2 gene, which is also referred to as neu. This protein is a member of a family of four receptors known as the epidermal growth factor receptors (EGFRs). These receptors are proteins that transmit signals from the outside of a cell to its interior, a process that directs many cellular functions.

Structurally, the HER2 protein has three main parts: an extracellular domain on the outside of the cell, a transmembrane segment that anchors it within the cell’s membrane, and an intracellular domain inside the cell. The intracellular portion contains tyrosine kinase activity, which is a mechanism for initiating signal transmission.

This placement on the cell surface positions the HER2 protein to receive and relay messages that influence cell behavior. Unlike its family members, researchers have not identified a specific molecule, or ligand, that binds directly to HER2’s extracellular domain to activate it. Instead, its activation is linked to its interactions with the other members of the EGFR family.

HER2 Signaling Mechanisms

The activation of HER2 occurs when it pairs up with other members of the ErbB receptor family. When a signaling molecule binds to a partner receptor like HER1 (EGFR) or HER3, it induces the formation of a partnership, known as a heterodimer, with HER2. This dimerization is the trigger that activates HER2’s kinase function. In situations where HER2 is present in high numbers, it can also form pairs with itself, called homodimers, which also leads to its activation.

Once activated, the tyrosine kinase portion of the HER2 protein adds phosphate groups to specific sites on its own tail. This process, known as autophosphorylation, creates docking sites for other proteins inside the cell. These adapter proteins and enzymes then become activated, setting off a chain reaction of signaling events.

This cascade of signals flows through several major pathways. One is the mitogen-activated protein kinase (MAPK) pathway, which is involved in regulating cell division and proliferation. Another route is the PI3K/AKT pathway, which plays a part in promoting cell survival, growth, and metabolism. The heterodimer formed between HER2 and HER3 is a potent activator of the PI3K/AKT pathway, driving messages of cell growth and survival.

Physiological Roles of HER2

The HER2 protein is an important component of normal human development, beginning in the embryonic stage. Its signaling activity is necessary for the proper formation of several tissues and organ systems, including the heart and the central nervous system.

In adult tissues, HER2 contributes to the body’s maintenance and repair processes. It participates in wound healing and ensures that cells divide and differentiate in a controlled manner to maintain tissue integrity. The signals transmitted by HER2 help regulate normal cell growth cycles and survival. For instance, HER2 receptors are found on heart muscle cells where they are important for cell survival, especially during times of stress.

Consequences of HER2 Dysregulation

Disruptions in the regulation of HER2 can lead to significant cellular problems. The most common form of dysregulation is the amplification of the ERBB2 gene, which results in an excessive number of HER2 proteins on the cell surface. This condition, known as HER2 overexpression, is a feature of certain cancers, including approximately 15-20% of breast cancers and a subset of gastric and esophageal cancers.

With an overabundance of HER2 receptors, the likelihood of them forming pairs with other ErbB family members and with themselves increases. This leads to a state of constitutive activation, where the receptors are constantly signaling, even without the external growth factors that would normally be required. This sustained signaling drives cells into a state of uncontrolled proliferation and growth.

The constant activation of downstream pathways, such as the MAPK and PI3K/AKT pathways, has profound effects on cell behavior. It promotes relentless cell division, helps cells evade programmed cell death (apoptosis), and can enhance their ability to invade surrounding tissues. Testing for HER2 status has become a standard diagnostic practice for cancers where its overexpression is common, as it provides information about the tumor’s potential aggressiveness.