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@ARTICLE{Brtsch:274322,
author = {S. M. Brütsch and E. Madzharova and S. Pantasis and T.
Wüstemann and S. Gurri and H. Steenbock and A. Gazdhar and
G. Kuhn and P. Angel$^*$ and S. Bellusci and J. Brinckmann
and U. Auf dem Keller and S. Werner and M. R. Bordoli},
title = {{M}esenchyme-derived vertebrate lonesome kinase controls
lung organogenesis by altering the matrisome.},
journal = {Cellular and molecular life sciences},
volume = {80},
number = {4},
issn = {1420-682X},
address = {Cham (ZG)},
publisher = {Springer International Publishing AG},
reportid = {DKFZ-2023-00536},
pages = {89},
year = {2023},
note = {DKFZ-ZMBH Alliance},
abstract = {Vertebrate lonesome kinase (VLK) is the only known secreted
tyrosine kinase and responsible for the phosphorylation of a
broad range of secretory pathway-resident and extracellular
matrix proteins. However, its cell-type specific functions
in vivo are still largely unknown. Therefore, we generated
mice lacking the VLK gene (protein kinase domain containing,
cytoplasmic (Pkdcc)) in mesenchymal cells. Most of the
homozygous mice died shortly after birth, most likely as a
consequence of their lung abnormalities and consequent
respiratory failure. E18.5 embryonic lungs showed a
reduction of alveolar type II cells, smaller bronchi, and an
increased lung tissue density. Global mass
spectrometry-based quantitative proteomics identified 97
proteins with significantly and at least 1.5-fold
differential abundance between genotypes. Twenty-five of
these had been assigned to the extracellular region and 15
to the mouse matrisome. Specifically, fibromodulin and
matrilin-4, which are involved in extracellular matrix
organization, were significantly more abundant in lungs from
Pkdcc knockout embryos. These results support a role for
mesenchyme-derived VLK in lung development through
regulation of matrix dynamics and the resulting modulation
of alveolar epithelial cell differentiation.},
keywords = {Collagen (Other) / Lung organogenesis (Other) / Pkdcc
(Other) / Proteomics (Other) / Skull (Other)},
cin = {A100},
ddc = {610},
cid = {I:(DE-He78)A100-20160331},
pnm = {311 - Zellbiologie und Tumorbiologie (POF4-311)},
pid = {G:(DE-HGF)POF4-311},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:36920550},
doi = {10.1007/s00018-023-04735-6},
url = {https://inrepo02.dkfz.de/record/274322},
}