Research demonstrated that differentiation of the mouse teratocarcinoma cell line F9 induced by retinoic acid is accompanied by major and specific alterations in the glycosylation of surface glycoproteins and suggest that the, changes may be due to modifications in activity of a few or perhaps a single glycosyltransferase. These studies do not, however, directly address many specific issues about the regulation of surface glycoprotein biosynthesis in animal cells. Little is actually known in detail about the structures of oligosaccharides at specific Asn-linked sugar sites of functional and normal cell surface glycoproteins (i.e. non- viral) and little is known about the factors that influence the glycosylation of surface proteins. Sugar addition is determined in part by the expression of appropriate glycosyltransferases an, glycosidases. However, several studies have shown that the primary sequences of protein can influence the glycosylation of the peptide at specific sites. To understand more about the factors regulating glycoprotein biosynthesis in F9 an, differentiated F9 cells, the glycosylation of a common surface glycoprotein, the transferrin receptor, will be investigated. The specific questions to be addressed in the proposed study are the following. (1) What are the structures of the chains at each Asn-linked glycosylation site on the receptor? (2) Does differentiation result in specific differences in the glycosylation of the receptor? (3) If changes are found to occur in the structures of the chain upon differentiation, how soon following the addition of retinoic acid are these change, observable? (4) Do the complex- type Asn-linked chains on the receptor have structures representative of the major types of chains derived from total glycoproteins? (5) If changes do occur in receptor glycosylation upon differentiation, do these changes affect the binding affinity of the receptor for transferrin or the turnover or recycling rate of the receptor? Answers to all these types of questions are not known for any surface glycoprotein in differentiating animal cells. Success in these studies will increase our knowledge of those factors influencing cell surface glycoprotein biosynthesis and should have broad implications for studies on other surface glycoproteins.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA037626-06
Application #
3175420
Study Section
Pathobiochemistry Study Section (PBC)
Project Start
1988-07-01
Project End
1991-03-31
Budget Start
1990-04-01
Budget End
1991-03-31
Support Year
6
Fiscal Year
1990
Total Cost
Indirect Cost
Name
University of Georgia
Department
Type
Schools of Arts and Sciences
DUNS #
City
Athens
State
GA
Country
United States
Zip Code
30602
Stray, S J; Cummings, R D; Air, G M (2000) Influenza virus infection of desialylated cells. Glycobiology 10:649-58
White, K D; Cummings, R D; Waxman, F J (1997) Ig N-glycan orientation can influence interactions with the complement system. J Immunol 158:426-35
Prieto, P A; Larsen, R D; Cho, M et al. (1997) Expression of human H-type alpha1,2-fucosyltransferase encoding for blood group H(O) antigen in Chinese hamster ovary cells. Evidence for preferential fucosylation and truncation of polylactosamine sequences. J Biol Chem 272:2089-97
Zheng, Z; Cummings, R D; Pummill, P E et al. (1997) Growth as a solid tumor or reduced glucose concentrations in culture reversibly induce CD44-mediated hyaluronan recognition by Chinese hamster ovary cells. J Clin Invest 100:1217-29
Yan, L; Wilkins, P P; Alvarez-Manilla, G et al. (1997) Immobilized Lotus tetragonolobus agglutinin binds oligosaccharides containing the Le(x) determinant. Glycoconj J 14:45-55
Yeh, J; Cummings, R D (1997) Differential recognition of glycoprotein acceptors by terminal glycosyltransferases. Glycobiology 7:241-51
Li, S; Neethling, F A; Yeh, J C et al. (1996) Potent inhibition of human and baboon anti-alpha Gal antibodies by a subfraction of oligosaccharides derived from porcine stomach mucin. Transplant Proc 28:558
DeBose-Boyd, R A; Nyame, A K; Smith, D F et al. (1996) alpha1,4-Fucosyltransferase activity in human serum and saliva. Arch Biochem Biophys 335:109-17
Cho, M; Cummings, R D (1996) Characterization of monomeric forms of galectin-1 generated by site-directed mutagenesis. Biochemistry 35:13081-8
Cho, S K; Yeh, J; Cho, M et al. (1996) Transcriptional regulation of alpha1,3-galactosyltransferase in embryonal carcinoma cells by retinoic acid. Masking of Lewis X antigens by alpha-galactosylation. J Biol Chem 271:3238-46

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