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An autocatalytic cleavage in the C terminus of the human MUC2 mucin occurs at the low pH of the late secretory pathway.

An autocatalytic cleavage in the C terminus of the human MUC2 mucin occurs at the low pH of the late secretory pathway. Research Abstract Details 

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  • An autocatalytic cleavage in the C terminus of the human MUC2 mucin occurs at the low pH of the late secretory pathway. Abstract Text:

    martin e lidellMartin E Lidell,malin e v johanssonMalin E V Johansson,gunnar c hanssonGunnar C Hansson,

    During purification of a recombinant MUC2 C terminus expressed in CHO-K1 cells, the protein was partly cleaved when buffers with a pH of 6.0 were used. When buffers with higher pH values were used, less cleavage was found. Disulfide bonds held the two fragments generated together as these were only observed after reduction. Edman sequencing of the C-terminal 110-kDa fragment revealed that the cleavage had occurred at an Asp-Pro bond, a site described previously to generate the so-called "link peptide" after disulfide bond reduction. In vitro studies on the conditions for cleavage showed that it occurred in a time-dependent manner at a pH below 6.0. Furthermore, the reaction was not enzyme-mediated as it occurred in pure preparations of the MUC2 C terminus and was not inhibited by protease inhibitors. When expressed in the mucin producing cell line LS 174T, the C terminus was cleaved to a higher extent compared with the CHO-K1 cells. Neutralizing the secretory pathway with either NH(4)Cl or bafilomycin A1 inhibited this cleavage. Altogether, our results suggest that the cleavage is an autocatalytic reaction that occurs in the acidic environment of the late secretory pathway. Furthermore, the cleavage produced a new, reactive C terminus that has the potential to attach the mucin to itself or other molecules. Because a pH below 6 can be reached in the late secretory pathway and on mucosal surfaces, the cleavage and possible cross-linking are likely to be of biological importance.

    An autocatalytic cleavage in the C terminus of the human MUC2 mucin occurs at the low pH of the late secretory pathway. Publishing Authors By Initials

    me lidellME Lidell,me johanssonME Johansson,gc hanssonGC Hansson,

    For similar natural sciences: time: time factors research abstracts see: natural sciences: time: time factors research

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    An autocatalytic cleavage in the C terminus of the human MUC2 mucin occurs at the low pH of the late secretory pathway. Journal Published:

    PUBLICATION TYPE: Research Support, Non-U.S. Gov

    Journal: The Journal of biological chemistry

    VOLUME: 278

    Page Numbers: 13944-51

    Journal Abbreviation: J. Biol. Chem.

    ISSN: 0021-9258

    DAY: 11

    MONTH: 02

    YEAR: 2003

    An autocatalytic cleavage in the C terminus of the human MUC2 mucin occurs at the low pH of the late secretory pathway. Information

    Number of References:

    LANGUAGE: eng

    NlmUniqueID: 2985121

    An autocatalytic cleavage in the C terminus of the human MUC2 mucin occurs at the low pH of the late secretory pathway. Keywords Mesh Terms:

    KEYWORDS: Time Factors

    MESH TERMS: metabolism

    Chemical & Substance for Abstract: An autocatalytic cleavage in the C terminus of the human MUC2 mucin occurs at the low pH of the late secretory pathway. Information

    Substance Name: bafilomycin A1

    Registry Number: 88899-55-2

    Grant and Affiliation Information for An autocatalytic cleavage in the C terminus of the human MUC2 mucin occurs at the low pH of the late secretory pathway.

    AFFILIATION: Department of Medical Biochemistry, Göteborg University, Medicinaregatan 9A, Sweden.

    Country: United States

    United States Research PublicationUnited States Research Publication

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    MEDLINETA: J Biol Chem

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