Lay Summary

Proposal No.   IBD-0026
Principal Investigator: Laurie L. Shekels, Ph.D.
Applicant Organization: University of Minnesota (Minneapolis, U.S.A.)
Project Title:  Does phosphorylation play a role in the function of the MUC3-related mucins?
Period of Award:  November 1, 2002 - February 29, 2004

Ulcerative colitis and Crohn’s disease are inflammatory diseases of the intestine collectively known as inflammatory bowel disease (IBD).  It has been established that there is a genetic component to IBD and several sites on chromosomes have been identified as conferring susceptibility to IBD.  The genes for several related proteins are found at one of these sites.  These proteins belong to a family of proteins called mucins.  Mucins are the major proteins in the mucous gel lining the intestine and are partly responsible for protecting the intestinal cells from dehydration, invasive bacteria and other forms of damage.  Some mucins are secreted from the intestinal cell, while others are inserted into the cell membrane.  Alterations in mucin type and quantity have been found in tissue from IBD patients.

This proposal focuses on the MUC3 family of membrane bound mucins and their function, with the novel suggestion that they may play a role in cell signaling during the inflammatory process.  We will examine whether the membrane bound mucins associate with other proteins and if they are modified by phosphorylation, a process that involved adding a phosphate group to an amino acid in the protein.  Phosphorylation of proteins is an important method used by cells to transmit signals or information from one part of the cell to another.

Phosphorylation may also alter the ability of a protein to interact with another protein.  In addition, DNA from patients with IBD will be examined for differences in the genes for the membrane bound mucins that may alter their ability to interact with another protein or to be phosphorylated and, thereby, alter their function.

There has been much emphasis on the immune cells involved in IBD.  This proposal focuses on other proteins in the intestinal cells.  In addition, it presents these mucin proteins not just as passive cellular particles, but also as active players involved in cell function during inflammation.  Understanding how these mucin proteins help the cell during inflammation may further the understanding of IBD clinical symptoms and may suggest new therapeutic approaches to IBD.