Epithelial surfaces are protected by a slimy, visco-elastic coat termed mucus. This layer is the first line of defense against mechanical, microbial or chemical insult to the underlying tissues. Of particular functional significance are the highly glycosylated, mucin-glycoproteins. These molecules are responsible for the unique rheological properties of the mucus coat. Many of the symptoms which characterize xerostomia including mucosal ulceration, increased incidences of plaque mediated disease and atypical oral infections have been linked to either a quantitative lack of or qualitative change in salivary mucin. Our approach to this problem has been to study the regulation of normal mucin- glycoprotein biosynthesis. In this way we hope to gain insight into the mechanisms which may underlie specific forms of salivary dysfunction. We propose to: (1) construct and characterize cDNAs which code for the protein core of rat submandibular gland mucin- glycoprotein (MG), (2) determine levels of mRNA coding for the apo-mucin and the glutamine/glutamic acid rich proteins (GRP), which are another class of abundant proteins found in the rat submandibular gland, (3) define the biosynthetic pathway for both the MG and GRP and, (4) continue clarification of the structure and organization of genes which code for the GRP.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
5R01DE008108-03
Application #
3221883
Study Section
Oral Biology and Medicine Study Section (OBM)
Project Start
1986-09-01
Project End
1990-06-30
Budget Start
1988-07-01
Budget End
1989-06-30
Support Year
3
Fiscal Year
1988
Total Cost
Indirect Cost
Name
University of Rochester
Department
Type
School of Medicine & Dentistry
DUNS #
208469486
City
Rochester
State
NY
Country
United States
Zip Code
14627
Ten Hagen, Kelly G; Balys, Marlene M; Tabak, Lawrence A et al. (2002) Analysis of isoproterenol-induced changes in parotid gland gene expression. Physiol Genomics 8:107-14
Ten Hagen, K G; Bedi, G S; Tetaert, D et al. (2001) Cloning and characterization of a ninth member of the UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase family, ppGaNTase-T9. J Biol Chem 276:17395-404
Kingsley, P D; Hagen, K G; Maltby, K M et al. (2000) Diverse spatial expression patterns of UDP-GalNAc:polypeptide N-acetylgalactosaminyl-transferase family member mRNAs during mouse development. Glycobiology 10:1317-23
Ten Hagen, K G; Tetaert, D; Hagen, F K et al. (1999) Characterization of a UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase that displays glycopeptide N-acetylgalactosaminyltransferase activity. J Biol Chem 274:27867-74
Hagen, F K; Hazes, B; Raffo, R et al. (1999) Structure-function analysis of the UDP-N-acetyl-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase. Essential residues lie in a predicted active site cleft resembling a lactose repressor fold. J Biol Chem 274:6797-803
Ten Hagen, K G; Hagen, F K; Balys, M M et al. (1998) Cloning and expression of a novel, tissue specifically expressed member of the UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase family. J Biol Chem 273:27749-54
Hagen, F K; Nehrke, K (1998) cDNA cloning and expression of a family of UDP-N-acetyl-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase sequence homologs from Caenorhabditis elegans. J Biol Chem 273:8268-77
Nehrke, K; Hagen, F K; Tabak, L A (1998) Isoform-specific O-glycosylation by murine UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase-T3, in vivo. Glycobiology 8:367-71
Nehrke, K; Ten Hagen, K G; Hagen, F K et al. (1997) Charge distribution of flanking amino acids inhibits O-glycosylation of several single-site acceptors in vivo. Glycobiology 7:1053-60
Nehrke, K; Tabak, L A (1997) Biosynthesis of a low-molecular-mass rat submandibular gland mucin glycoprotein in COS7 cells. Biochem J 323 ( Pt 2):497-502

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