Title : Post-translational processing of membrane-associated recombinant human
stem cell factor expressed in Chinese hamster ovary cells
Abstract :
- This report describes the structure of soluble human stem cell factor isolated from the conditioned medium of Chinese hamster ovary (CHO) cells transfected with stem cell factor ( SCF ) cDNA, which encodes a leader sequence plus 248 additional amino acids
- The 248 amino acids include a hydrophobic transmembrane region at positions 190-212
- The isolated material is glycosylated and three bands (apparent M(r) 28,000, M(r) 35,000, and M(r) 40,000) are evident by sodium dodecyl sulfate ( SDS )-polyacrylamide gel electrophoresis
- After complete deglycosylation, the molecular weight by SDS-polyacrylamide gel electrophoresis is 18,000-19,000
- Structural analyses of the intact SCF , the deglycosylated SCF , and a deglycosylated C-terminal peptide were performed by laser desorption, fast atom bombardment, or electrospray mass spectrometry
- Pulse-labeling of cells with 35S-labeled Met and Cys resulted in cell-associated glycosylated SCF of M(r) 33,000-45,000 which was converted to M(r) 33,000 by in vitro treatment with glycosidases
- During a chase with unlabeled Met and Cys , labeled SCF of M(r) 28,000, M(r) 35,000, and M(r) 40,000 appeared in the medium; it was converted to M(r) 18,000-19,000 by glycosidase treatment
- SCF at the surface of the transfected CHO cells could be demonstrated by immunofluorescence
- The data obtained indicate that the recombinant human stem cell factor , as isolated, represents proteolytically processed forms containing amino acids 1-165, derived from the initially synthesized membrane-bound form of 248 amino acids
- Further characterization indicated that the M(r) 28,000 form is glycosylated at Asn120 , the M(r) 35,000 form at Asn120 and Asn65 , and the M(r) 40,000 form at Asn120, Asn93, and Asn65
- Each form also contains O-linked carbohydrate
- The N-linked glycosylation, particularly that at Asn93 and at Asn65 , adversely affects in vitro biological activity and receptor binding
Output (sent_index, trigger,
protein,
sugar,
site):
- 10. glycosylated, , -, -, Asn120, Asn93, and Asn65
- 10. glycosylated, , -, -, Asn120
- 12. glycosylation, , receptor, -, -
- 5. deglycosylated, , -, -, peptide
- 5. deglycosylated, , SCF, -, -
- 6. glycosylated, , SCF, -, -
Output(Part-Of) (sent_index,
protein,
site):
*Output_Site_Fusion* (sent_index,
protein,
sugar,
site):
- 10. stem cell factor, -, Asn120, Asn93, and Asn65
- 10. stem cell factor, -, Asn120