Characterization of a cysteine proteinase inhibitor induced during neuronal cell differentiation.

Full Abstract

A rat homolog of human cystatin E/M was identified by differential display of transcripts induced during neuronal cell differentiation. A member of the family 2 cystatins, rat cystatin E/M is secreted, glycosylated and developmentally regulated. Rat cystatin E/M is expressed in brain, and is induced during differentiation of a conditionally immortalized E17 rat hippocampal cell line (H19-7) by bFGF or activated Raf via MEK-dependent and -independent signaling pathways. Rat cystatin E/M protein is increased post-transcriptionally in PC12 cells, and the protein is secreted into the medium of primary embryonal hippocampal cultures. Analysis of the K (i) of recombinant His-tagged rat cystatin E/M toward cathepsins B and H revealed that rat cystatin E/M has an inhibitor profile distinct from that of other members of the cystatin family. Motif swapping between rat cystatin E/M and human cystatin C, a well-characterized cystatin, identified some residues that can contribute to the specificity of inhibition. Taken together, these results describe a member of the cystatin family that has a distinct inhibitor profile and may play a role in neuronal development.

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Author information

Author/s: Hong, Jia (J); Yoshida, Keiko (K); Rosner, Marsha Rich (MR);

Affiliation: Department of Neurobiology, Pharmacology and Physiology, University of Chicago, Chicago, Illinois 60637, USA.

Grants: NS 33858 (Agency:United States NINDS)

Journal and publication information

Publication Type: Journal Article; Research Support, U.S. Gov't, P.H.S.

Journal: Journal of neurochemistry (J Neurochem), published in England. (Language: eng)

Reference: 2002-Jun; vol 81 (issue 5) : pp 922-34

Dates: Created 2002/06/14; Completed 2002/07/09; Revised 2007/11/14;

PMID: 12065604, status: MEDLINE (last retrieval date: 11/6/2008)

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Animals
Base Sequence
Cathepsins - antagonists & inhibitors
Cell Differentiation - physiology
Cells, Cultured
Cloning, Molecular
Cystatins - genetics; metabolism; secretion
Cysteine Proteinase Inhibitors - genetics; metabolism
Enzyme Activation - drug effects
Enzyme Inhibitors - pharmacology
Gene Expression Profiling
Gene Expression Regulation

Gene Expression Regulation, Developmental
Glycosylation
Hippocampus - metabolism
Humans
Mitogen-Activated Protein Kinase Kinases - metabolism
Molecular Sequence Data
Neurons - cytology; metabolism
Organ Specificity
PC12 Cells
Rats
Recombinant Fusion Proteins - genetics; metabolism
Sequence Homology, Amino Acid

Associated Chemicals: Cystatins (0) ; Cysteine Proteinase Inhibitors (0) ; Enzyme Inhibitors (0) ; Recombinant Fusion Proteins (0) ; cystatin E (0) ; Mitogen-Activated Protein Kinase Kinases (EC 2.7.1.-) ; Cathepsins (EC 3.4.-)

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