CD109 is a protein found on the surface of various cells in the human body. It is a subject of ongoing scientific investigation due to its involvement in biological processes. Research suggests it regulates cellular signals, influencing various aspects of health and disease. Understanding CD109’s functions offers insights into how the body maintains balance and responds to challenges like inflammation and abnormal cell growth.
What is CD109 and Where is it Found?
CD109 is a cell surface glycoprotein, a protein with attached sugar chains on the outer membrane of cells. It is a member of the alpha-2-macroglobulin/C3, C4, C5 family of thioester-containing proteins, known for roles in the immune system. The full-length CD109 protein is composed of 1445 amino acids and has a predicted molecular mass of approximately 162 kilodaltons. It possesses a C-terminal signal sequence that allows it to be anchored to the cell surface by a glycosylphosphatidylinositol (GPI) anchor.
CD109 is found in a variety of cell types throughout the body. It is expressed on platelets, small blood cells that help form clots. CD109 is also present on activated T-cells, a type of white blood cell central to the immune system’s response to infections and diseases. Furthermore, it is found on endothelial cells, which line blood vessels and regulate blood flow and immune cell movement. Its expression has also been noted in keratinocytes, the main cell type found in the outer layer of the skin.
How CD109 Influences Cell Signals
A primary function of CD109 is to negatively regulate the Transforming Growth Factor-beta (TGF-beta) signaling pathway. TGF-beta is a powerful signaling pathway that orchestrates many cellular activities, including cell growth, differentiation, and immune response regulation. It is a versatile cytokine, a protein messenger between cells, and its proper regulation is important for maintaining tissue health.
CD109 influences this pathway by acting as a co-receptor for TGF-beta. It interacts with TGF-beta signaling receptors, promoting their movement into specific cell surface compartments called caveolae. This action dampens the TGF-beta signal.
CD109 also inhibits TGF-beta signaling by enhancing the degradation of TGF-beta receptors. It promotes the degradation of the type I TGF-beta receptor (TGFBR1) through a process that involves other proteins like SMAD7 and Smurf2. By facilitating the breakdown of these receptors, CD109 reduces the number of receptors available on the cell surface to bind TGF-beta, thereby limiting the downstream cellular responses to TGF-beta. This regulation of receptor availability and degradation contributes to CD109’s overall ability to modulate the strength and duration of TGF-beta signaling within cells.
CD109’s Connection to Health and Illness
CD109’s influence on cell signaling pathways, particularly its regulation of TGF-beta, has significant implications for human health and disease. Its involvement is notable in inflammatory responses and various forms of cancer.
In inflammatory conditions like rheumatoid arthritis, CD109 is found in abundance in affected tissues and its expression can be heightened by inflammatory signals. Reducing CD109 levels or blocking its activity has been shown to decrease pro-inflammatory factor production, cell migration, and other aspects of the inflammatory response in laboratory settings.
CD109 also plays a role in the immune system’s overall balance. It affects the differentiation and function of T helper cells, which are a type of immune cell that helps coordinate the body’s defense against pathogens. For instance, certain T helper cells expressing CD109 produce interleukin-10 (IL-10), a cytokine known for its immunosuppressive properties, which helps to prevent excessive inflammation and maintain immune equilibrium. CD109’s modulation of TGF-beta signaling and its impact on cytokine production are thought to contribute to preventing overactive immune responses and autoimmune conditions.
In cancer, CD109 expression is frequently observed at high levels in various malignant tumors, including squamous cell carcinomas in the esophagus, uterus, and lung, and also in pancreatic cancer. This overexpression is often linked to a more aggressive tumor phenotype and a less favorable prognosis. CD109 can contribute to tumor progression by influencing different signaling pathways beyond TGF-beta, such as the epidermal growth factor receptor (EGFR)/AKT/mTOR pathway and the JAK/STAT3 pathway, both of which are involved in cell growth, survival, and migration. In some cancers, CD109 can enhance cancer cell migration and proliferation, suggesting it may promote tumor development and spread.