Target intelligence / Profile preview

Granulocyte-macrophage colony-stimulating factor receptor (GM-CSF receptor) (GM-CSFR)

Target
GM-CSFR
Molecular classification
Receptor, Cytokine receptor, Type I cytokine receptor
01

Overview

The granulocyte-macrophage colony-stimulating factor receptor (GM-CSFR) is a type I transmembrane cytokine receptor comprised of an α subunit (CD116) which binds the GM-CSF ligand, and a βc (common) subunit which transduces intracellular signaling. Receptor activation leads to phosphorylation events that recruit and activate downstream signaling proteins, including JAK2, STAT5, ERK, and PI3K, orchestrating cell survival, proliferation, and differentiation. GM-CSFR plays a central role in hematopoiesis, immune regulation, and inflammatory responses, and is implicated in various diseases including inflammatory disorders, autoimmune diseases, cancers of myeloid origin, and some neurodegenerative conditions. Drugs targeting this receptor, including agonists and antagonists, are used or under investigation for a range of hematologic and immune-mediated conditions.

Other names
CSF2 receptorGM-CSF receptor alpha and beta subunitsColony-stimulating factor 2 receptorCD116 (alpha subunit)Beta common receptor (shared βc subunit with IL-3 and IL-5 receptors)
02

Mechanism of action

Cytokine binding induces receptor dimerization/multimerization and activation Triggering of JAK2/STAT5, MAPK, PI3K, and NF-κB signaling pathways Modulation of immune cell survival, proliferation, differentiation, and activation

03

Biological functions

Regulation of myeloid cell proliferationRegulation of survival and differentiation of granulocytes and macrophagesImmune response modulationInflammatory signalingCell signaling (JAK/STAT, MAPK, PI3K pathways)
04

Disease associations

InflammationAutoimmune diseasesCancer (especially myeloid leukemias and solid tumors)InfectionPulmonary diseases (e.g., pulmonary alveolar proteinosis)Neurodegenerative disease (due to microglia regulation)
05

Safety considerations

Myeloproliferation and leukocytosis (with agonists)Cytokine release syndromeRisk of inflammation/exacerbation of autoimmune or inflammatory diseasesNeutropenia or impaired host defense with antagonists/antibodiesPotential off-target effects due to broad receptor expression
06

Interacting drugs

Sargramostim (recombinant human GM-CSF)

4 more in the full profile.

07

Biomarkers

GM-CSF or GM-CSFR expression on myeloid lineage cellsPhosphorylated STAT5CD116 (surface marker)Increased cytokine levels as markers for patient selection/therapeutic response

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