G-CSF Receptor, Recombinant, Human (G-CSFR, GCSFR, CSF3R, Granulocyte Colony-stimulating Factor Rece

Granulocyte Colony Stimulating Factor (G­CSF) is a pleiotropic cytokine best known for its specific effects on the proliferation, differentiation, and activation of hematopoietic cells of the neutrophilic granulocyte lineage. G­CSF plays an important role in defense against infection, in inflammation and repair, and in the maintenance of steady state hematopoiesis. Recombinant human G­CSF has been approved for the amelioration of chemotherapy induced neutropenia as well as for severe chronic neutropenia following marrow transplant., Cell activation by G­CSF is mediated by a type I membrane protein belonging to the cytokine receptor superfamily. Human G­CSF R is 863 amino acids (aa) in length, with a 604 aa extracellular domain, a 26 aa transmembrane domain, and a 183 aa cytoplasmic domain that include a 23 amino acid signal sequence. As a result of alternative splicing, at least four isoforms of G­CSF R that differ in their C­terminal region exist. Isoform 2 lacks the transmembrane region and may represent a soluble form of the receptor, however the existence of soluble G­CSF R in human serum has not been reported (1). Mutations have been found in the gene encoding G­CSF 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 (2). Human and mouse G­CSF R have a homology of 62.5%. G­CSF R is expressed in mature neutrophils, neutrophilic precursors, myeloid leukemia cells, and placenta. Binding of G­CSF 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), src­related protein tyrosine kinases (Lyn and Syk), Ras/MAP kinase, and phosphatidylinositol have been reported to be activated upon G­CSF stimulation (1). , Recombinant protein corresponding to Glu25-Pro621 from human G-SCFR from murine myeloma cell line, NS0-derived. SDS­-PAGE: 95­105kD, reducing conditions, Activity: Measured by its ability to inhibit the G-CSF-induced proliferation of NFS-60 mouse myeloid cells. The ED50 is typically 1-4ug/ml in the presence of 0.125ng/ml of rhG-CSF. Storage and Stability: Lyophilized powder may be stored at -20°C. Stable for 12 months after receipt at -20°C. Reconstitute with sterile PBS. Aliquot to avoid repeated freezing and thawing. Store at -20°C. Reconstituted product is stable for 6 months at -20°C. For maximum recovery of product, centrifuge the original vial after thawing and prior to removing the cap. Further dilutions can be made in assay buffer.