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FLASH GENE
Symbol CSF2 contributors: mct - updated : 28-01-2019
HGNC name colony stimulating factor 2 (granulocyte-macrophage)
HGNC id 2434
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
conjugated GlycoP
mono polymer monomer
HOMOLOGY
interspecies homolog to murine Csf2
homolog to C.elegans y71f9b.1
Homologene
FAMILY
  • GM-CSF family
    • CATEGORY immunity/defense , signaling cytokine
    SUBCELLULAR LOCALIZATION extracellular
    basic FUNCTION
  • stimulating the growth and differentiation of hematopoietic precursor cells from various lineages (granulocytes, macrophages, eosinophils and erythrocytes)
  • in the absence of other cytokines sustains human dendritic cell precursors with T cell regulatory activity and capacity to differentiate into functional dendritic cells
  • CASC3 and CSF2 are involved in the proliferation of fibroblast-like synoviocytes in the pathogenesis of rheumatoid arthritis
  • CSF2 signaling activates mitogen-activated protein kinase, followed by the upregulation of CASC3 and CFLAP, resulting in fibroblast-like synoviocyte hyperplasia in rheumatoid arthritis
  • may accelerate cell growth and inhibit cell death via PKC activation in the cell lines and also seems to reverse growth suppression and cell death induced by PKC inhibition
  • IL2 and CSF2 are regulated by DNA demethylation during activation of T cells, B cells and macrophages
  • CSF2 is important in vaccine-induced CD8(+) T cell immunity through the regulation of nonlymphoid tissue Dendritic cells (DCs) homeostasis rather than control of inflammatory DCs
  • IL21 and CSF2 exhibit cross-regulatory actions on gene regulation and apoptosis, regulating conventional dendritic cells (cDCs) numbers and thereby the magnitude of the immune response
  • haemopoietic growth factor that is used in the clinic to correct neutropaenia, usually as a result of chemotherapy
  • is a key factor in Th17 driven autoimmune inflammatory conditions
  • CSF1 and CSF2 can regulate the development and function of the mononuclear phagocyte system (MPS)
  • has emerged as a crucial cytokine produced by auto-reactive T helper (Th) cells that initiate tissue inflammation
  • critical role in immune modulation and hematopoiesis
  • has inhibitory effects on tumor growth and metastasis, but also exerts stimulatory effects on tumor progression
    • CELLULAR PROCESS cell life, proliferation/growth
    PHYSIOLOGICAL PROCESS immunity/defense
    text control of cell proliferation
    PATHWAY
    metabolism
    signaling
  • CSF2 signaling controls a pathogenic expression signature in CCR2(+)Ly6C(hi) monocytes and their progeny, which was essential for tissue damage
    • a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • MMP2 and MMP14 (upregulated by CSF2 in head and neck cancer cells)
  • nuclear activation of REL not only regulates the initiation of CSF2 and IL2 gene activation in response to T cell activation, but also the termination of these gene responses following the removal of the activating signal
  • NFKB1 controls IL2 and CSF2 expression during T cell development and activation process
  • accelerated the G1/S phase transition in endothelial progenitor cells (EPCs) by upregulating the expression of CCND1 and CCNE1
  • CSF2 has a lung-specific role in the perinatal development of alveolar macrophages (AMs) through the induction of PPARG in fetal monocytes
  • TRAF6 is required for CSF2-induced ubiquitination and activation of AKT1
  • MAFB is a negative regulator of CSF2 signaling in microglia
  • RNF13 affects the concentration of CSF2 in tumor-bearing lungs, leading to a reduction in the colonization of metastatic tumor cells in the lung
  • upregulation of CSF2 and CSF1 production by endothelial cells, an effect that appears to be mediated by NFKB1 and to be independent of IL1, may be an additional mechanism through which IL33 contributes to inflammatory activation of the vessel wall
  • DPP4/CD26 enzymatically cleaves select penultimate amino acids of proteins, including colony-stimulating factors (CSF2), and has been implicated in cellular regulation
    • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    increased pulmonary CSF2 production in response to infection is primed by the microbiota through IL17A
    constitutional       gain of function
    in periodic fever, aphthous stomatitis, pharyngitis and cervical adenopathy syndrome with activation of IL8
    Susceptibility
  • to asthma
  • to rheumatoid arthritis
    • Variant & Polymorphism variant ile 117 maybe a risk factor for atopic asthma
    Candidate gene
    Marker
    Therapy target antibody specific for cytokine or receptor as therapeutic targets in rheumatoid arthritis
    ANIMAL & CELL MODELS
  • in Csf2 gene-deficient mice, a detailed kinetic analysis of monocyte/macrophage and neutrophil dynamics in antigen-induced peritonitis suggested that Csf2 was acting, in part, systemically to maintain the inflammatory reaction