| Autor: |
KANTOLA, ANNA K., RYYNÄNEN, MERJA J., LHOTA, FILIP, KESKI-OJA, JORMA, KOLI, KATRI |
| Předmět: |
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| Zdroj: |
Journal of Cellular Physiology; Jun2010, Vol. 223 Issue 3, p727-736, 10p, 1 Black and White Photograph, 3 Diagrams, 2 Graphs |
| Abstrakt: |
Transforming growth factor (TGF)-β is secreted and targeted into the extracellular matrix (ECM) in association with one of the latent TGF-β binding proteins (LTBPs). Activation of these latent complexes is an important regulatory step in TGF-β signaling. LTBPs target the growth factor into the ECM and expose it to activating mechanisms. Disruption of LTBP-4 gene causes severe developmental abnormalities in both humans and mice. Transcripts for two N-terminally distinct LTBP-4 variants, LTBP-4S (short) and -4L (long), have been identified. In the current work, we have characterized differences in the expression, processing, and ECM targeting of these LTBP-4 variants. Heart and skeletal muscle displayed expression of both variants, while liver expressed mainly LTBP-4L and lung as well as small intestine LTBP-4S. This tissue-specific expression pattern was found to originate from control of transcription by two independent promoters. Furthermore, LTBP-4S and -4L proteins were secreted and processed differently. During secretion, LTBP-4L was complexed with TGF-β1, whereas the majority of LTBP-4S was secreted in a free form. In addition, LTBP-4S was incorporated into the ECM, while full-length LTBP-4L was not readily detectable in the ECM. These data suggest that LTBP-4 functions are modified by tissue-specific expression of the two N-terminally distinct variants, which in addition exhibit significant differences in cellular processing and targeting, that is, this provides a basis for understanding molecular diversity in LTBP-4 structure and function. J. Cell. Physiol. 223:727–736, 2010. © 2010 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR] |
| Databáze: |
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