Title : Role of
carbohydrate modification in the production and secretion of human
granulocyte macrophage colony-stimulating factor in
genetically engineered and normal mesenchymal cells
Abstract :
- Colony-stimulating factors ( CSFs ) are a group of acidic glycoproteins which stimulate the proliferation and differentiation of hematopoietic progenitor cells in vitro and stimulate hemopoiesis in vivo
- Human GM-CSF contains two N-linked carbohydrate side chains of the complex acidic type and several sites of O-linked carbohydrate clustered on serine and threonine residues near the N-terminus of the molecule
- Previous studies have failed to detect a significant functional role for the carbohydrate modification characteristic of human GM-CSF
- Using permanent cell lines and transient expression systems which produce moderate to high levels of native or carbohydrate-deficient forms of the growth factor , the role of carbohydrate modification in the biosynthesis and secretion of GM-CSF was studied
- Unlike a number of other secreted glycoproteins , the transient time and secretory efficiency of several carbohydrate-deficient mutants of GM-CSF are indistinguishable from those of the native growth factor in BHK, 293, COS, and ldlD cells
- Furthermore, normal human endothelial cells and fibroblasts, which normally produce the growth factor , can synthesize and secrete GM-CSF that lacks all forms of carbohydrate modification.
- These studies help to point out the range of roles played by carbohydrate modification in the biosynthesis, assembly, and secretion of glycoprotein hormones