Granulocyte colony stimulating factor is a pleiotropic cytokine best known for its specific effects on the proliferation, differentiation, and activation of hematopoietic cells of the neutrophilic and granulocyte lineage.
G-CSF plays an important role in defense against infection, in inflammation and repair, and in the maintenance of steady state hematopoiesis.
Cell activation by G-CSF is mediated by granulocyte colony stimulating factor receptor alpha (G-CSF R; also CD114), a 95-105kD type I transmembrane protein and member of the cytokine receptor superfamily, type I cytokine receptor family, and type 2 subfamily of receptor proteins.
Mouse G-CSF R is synthesized as an 837aa precursor that contains a 25aa signal sequence, a 601aa extracellular domain a 24aa transmembrane region, and a 187aa cytoplasmic tail.
The ECD contains one Ig-like C2-type domain, five fibronectin type-III domains, and 11 potential sites for N-linked glycosylation.
Within the ECD there is also a WSXWS motif aa319-323 that is necessary for proper protein folding and thereby efficient intracellular transport and cell-surface receptor binding.
Also, within the cytoplasmic domain there is a Box 1 motif which is required for JAK interaction and/or activation.
Mouse G-CSF R shares 63% aa sequence identity with human G-CSF R.
G-CSF R is expressed in mature neutrophils, neutrophilic precursors, myeloid leukemia cells, and placenta.
Mutations have been found in the gene encoding G-CSF R in some patients with severe congenital neutropenia.
These mutations typically lead to a truncation in the cytoplasmic domain of the G-CSF R leading to maturation arrest of neutrophilic precursors in the bone marrow and neutropenia in peripheral blood.
Binding of G-CSF to its receptor induces dimerization or oligomerization of the receptor activating cytoplasmic tyrosine kinases.
Signal transduction from pathways that involve Janus tyrosine kinases/signal transducer and activator of transcription proteins (Jak1, Jak2, and Tyk2/STAT3 and STATG), src-related protein tyrosine kinases (Lyn and Syk), Ras/MAP kinase, and phosphatidylinositol have been reported to be activated upon G-CSF stimulation.
