CSF2RA

Colony-stimulating factor 2 receptor alpha (CSF2RA), also known as GM-CSF receptor alpha or CD116, forms a heterodimeric receptor with CSF2RB to mediate granulocyte-macrophage colony-stimulating factor (GM-CSF) signaling. This receptor complex activates JAK2/STAT5, MAPK/ERK, and PI3K/AKT pathways, regulating myeloid cell differentiation, proliferation, and immune responses. CSF2RA mutations are linked to pulmonary surfactant metabolism dysfunction (e.g., childhood interstitial lung disease) due to impaired alveolar macrophage function. Dysregulated CSF2RA expression is implicated in myeloid malignancies, particularly juvenile myelomonocytic leukemia and acute myeloid leukemia, where autocrine GM-CSF signaling drives leukemogenesis. Therapeutic strategies targeting the GM-CSF/CSF2RA axis include monoclonal antibodies (e.g., mavrilimumab) in phase II trials for rheumatoid arthritis and GM-CSF-neutralizing agents like lenzilumab for COVID-19-associated hyperinflammation. Small-molecule inhibitors disrupting CSF2RA-JAK2 interactions are under preclinical evaluation for hematologic cancers.