Recombinant Human G-CSFR/CD114 Protein

Granulocyte Colony Stimulating Factor (G-CSF) is a pleiotropic cytokine best known for its specific effects on the proliferation, differentiation, and activation of hematopoietic cells of the neutrophilic granulocyte lineage (1). G-CSF plays an important role in defense against infection, in inflammation and repair, and in the maintenance of steady state hematopoiesis. Recombinant human G-CSF has been approved for the amelioration of chemotherapy induced neutropenia as well as for severe chronic neutropenia following marrow transplant.

Cell activation by G-CSF is mediated by a type I membrane protein belonging to the cytokine receptor superfamily. Human G-CSF R is 836 amino acids (aa) in length, with 24 amino acid signal sequence, a 603 aa extracellular domain, a 23 aa transmembrane domain, and a 186 aa cytoplasmic domain. As a result of alternative splicing, at least four isoforms of G-CSF R that differ in their C-terminal region exist. Isoform 2 lacks the transmembrane region and may represent a soluble form of the receptor. The existence of 80 & 85 kDa forms of soluble G-CSF R in human serum has been reported (2). Mutations have been found in the gene encoding G-CSF R in some patients with severe congenital neutropenia. These mutations typically led to a truncation in the cytoplasmic domain of the G-CSF R leading to maturation arrest of neutrophil precursors in the bone marrow and neutropenia in peripheral blood (3). Human and mouse G-CSF R have a homology of 62.5%.

G-CSF R is expressed in mature neutrophils, neutrophilic precursors, myeloid leukemia cells, and placenta. 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, 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 (1).