The polymeric immunoglobulin receptor transports the polymeric immunoglobulins, IgA and IgM (pIg) into a wide variety of mucosal secretions, including bile. These antibodies form the first line of immunologic defense against infection, and their transport is deranged in several diseases. The pIg receptor (pIg-R) undergoes a variety of sorting steps in its transport across the cell. Many of these steps are mediated by proteins that interact with the cytoplasmic tail of the pIg-R. The goal of this research is to identify and characterize proteins from rat liver that bind to this cytoplasmic tail and mediate sorting. The cytoplasmic tail has been expressed as a recombinant protein fragment in E. coli, purified with a monoclonal antibody, and coupled to a solid matrix for affinity chromatography. In preliminary experiments cytosolic proteins from Madin-Darby canine kidney cells have been passed over this matrix, and several proteins that specifically bind to the tail of pIg-R have been identified. However, it is difficult to purify useful amounts of these proteins from these cultured cells. Rat liver expresses very large amounts of the pIg-R, and so cytosolic proteins from rat liver will be used in this pilot study as a source to purify useable quantities of these proteins. Moreover, well-characterized endosomal membrane fractions from rat liver may also contain other proteins that interact with the pIg-R cytoplasmic tail. Therefore, we will prepare non-denaturing detergent extracts of these membranes which will also be used as starting material for affinity chromatography. These proteins will be used for raising antibodies, which will be used for immunocytochemical localization. These antibodies will also be used to clone cDNA's for these proteins, which will be sequenced. Finally, the biochemical functions of these proteins will be studied in a variety of in vivo and in vitro assays.

Project Start
Project End
Budget Start
Budget End
Support Year
15
Fiscal Year
1995
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Type
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Schwartz, Janice B; Gallagher, J Christopher; Jorde, Rolf et al. (2018) Determination of Free 25(OH)D Concentrations and Their Relationships to Total 25(OH)D in Multiple Clinical Populations. J Clin Endocrinol Metab 103:3278-3288
Qiao, Yu; Xu, Meng; Tao, Junyan et al. (2018) Oncogenic potential of N-terminal deletion and S45Y mutant ?-catenin in promoting hepatocellular carcinoma development in mice. BMC Cancer 18:1093
Sarkar, Monika; Terrault, Norah; Duwaerts, Caroline C et al. (2018) The Association of Hispanic Ethnicity with Nonalcoholic Fatty Liver Disease in Polycystic Ovary Syndrome. Curr Opin Gynecol Obstet 1:24-33
Benet, Leslie Z; Bowman, Christine M; Liu, Shufang et al. (2018) The Extended Clearance Concept Following Oral and Intravenous Dosing: Theory and Critical Analyses. Pharm Res 35:242
Verstraete, Sofia G; Wojcicki, Janet M; Perito, Emily R et al. (2018) Bisphenol a increases risk for presumed non-alcoholic fatty liver disease in Hispanic adolescents in NHANES 2003-2010. Environ Health 17:12
Dave, S; Dodge, J L; Terrault, N A et al. (2018) Racial and Ethnic Differences in Graft Loss Among Female Liver Transplant Recipients. Transplant Proc 50:1413-1423
Maher, Jacquelyn J (2018) Macrophages Steal STING From the Infectious Disease Playbook to Promote Nonalcoholic Fatty Liver Disease. Gastroenterology 155:1687-1688
Cullaro, Giuseppe; Park, Meyeon; Lai, Jennifer C (2018) ""Normal"" Creatinine Levels Predict Persistent Kidney Injury and Waitlist Mortality in Outpatients With Cirrhosis. Hepatology 68:1953-1960
Lee, Brian P; Mehta, Neil; Platt, Laura et al. (2018) Outcomes of Early Liver Transplantation for Patients With Severe Alcoholic Hepatitis. Gastroenterology 155:422-430.e1
Campos-Varela, Isabel; Agudelo, Eliana Z; Sarkar, Monika et al. (2018) Use of a hepatitis C virus (HCV) RNA-positive donor in a treated HCV RNA-negative liver transplant recipient. Transpl Infect Dis 20:

Showing the most recent 10 out of 1119 publications