CSF1R

Colony stimulating factor 1 receptor
Identifiers
Symbol	?
NCBI gene	1436
HGNC	2432
OMIM	164770
RefSeq	NM_005211
UniProt	P07333
Search for Structures Swiss-model Domains InterPro

Colony stimulating factor 1 receptor (CSF1R) is a protein that in humans is encoded by the CSF1R gene. This receptor is a member of the tyrosine kinase family of receptors and plays a crucial role in the regulation of macrophage production, differentiation, and function.

Structure

CSF1R is a transmembrane receptor that consists of an extracellular domain, a single transmembrane helix, and an intracellular tyrosine kinase domain. The extracellular domain is responsible for binding its ligand, colony stimulating factor 1 (CSF1), also known as macrophage colony-stimulating factor (M-CSF), and interleukin 34 (IL-34).

Function

CSF1R is primarily expressed on the surface of monocytes, macrophages, and their precursors. Upon binding to its ligands, CSF1R undergoes dimerization and autophosphorylation, which activates its kinase activity. This activation triggers a cascade of downstream signaling pathways, including the PI3K/AKT and MAPK/ERK pathways, which are involved in cell survival, proliferation, and differentiation.

Role in Disease

Mutations in the CSF1R gene have been associated with several diseases. Notably, hereditary diffuse leukoencephalopathy with spheroids (HDLS) is a rare neurodegenerative disorder caused by mutations in CSF1R. This condition is characterized by white matter degeneration and the presence of axonal spheroids.

CSF1R is also implicated in various cancers, as its overexpression can lead to increased macrophage infiltration and tumor progression. Targeting CSF1R with specific inhibitors is being explored as a therapeutic strategy in cancer treatment.

Clinical Significance

CSF1R inhibitors are being developed and tested in clinical trials for their potential to treat cancers and inflammatory diseases. These inhibitors aim to modulate the tumor microenvironment by reducing the number of tumor-associated macrophages, which can promote tumor growth and metastasis.

Research Directions

Ongoing research is focused on understanding the precise mechanisms by which CSF1R signaling influences immune cell behavior and its role in various pathological conditions. The development of more selective and potent CSF1R inhibitors is also a key area of interest.

See also

• Macrophage
• Tyrosine kinase
• Colony stimulating factor 1
• Interleukin 34

External links

• CSF1R gene - NCBI
• CSF1R protein - UniProt