PDGFRA

PDGFRA

The PDGFRA gene provides instructions for making a protein called platelet-derived growth factor receptor alpha (PDGFRA), which is part of a family of proteins called receptor tyrosine kinases (RTKs). Receptor tyrosine kinases transmit signals from the cell surface into the cell through a process called signal transduction. The PDGFRA protein is found in the cell membrane of certain cell types where a specific protein, called platelet-derived growth factor, attaches (binds) to it. This binding turns on (activates) the PDGFRA protein, which then activates other proteins inside the cell by adding a cluster of oxygen and phosphorus atoms (a phosphate group) at specific positions (a process called phosphorylation). This process leads to the activation of a series of proteins in multiple signaling pathways.

The signaling pathways stimulated by the PDGFRA protein control many important cellular processes such as cell growth and division (proliferation) and cell survival. PDGFRA protein signaling is important for the development of many types of cells throughout the body.

Mutations in the PDGFRA gene are also associated with gastrointestinal stromal tumors (GISTs). GISTs are a type of tumor that occurs in the gastrointestinal tract, most commonly in the stomach or small intestine. The majority of GISTs associated with a mutation in the PDGFRA gene occur in the stomach. In most cases, the genetic changes are acquired during a person's lifetime and are called somatic mutations. Somatic mutations, which lead to sporadic GISTs, are present only in the tumor cells and are not inherited. Less commonly, PDGFRA gene mutations that increase the risk of developing GISTs are inherited from a parent, which can lead to familial GISTs.

PDGFRA gene mutations associated with GISTs create a protein that no longer requires binding of the platelet-derived growth factor protein to be activated. As a result, the PDGFRA protein and the signaling pathways are constitutively activated, which increases cell proliferation and survival, leading to tumor formation.

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