TY  - JOUR
AU  - Brütsch, Salome M
AU  - Madzharova, Elizabeta
AU  - Pantasis, Sophia
AU  - Wüstemann, Till
AU  - Gurri, Selina
AU  - Steenbock, Heiko
AU  - Gazdhar, Amiq
AU  - Kuhn, Gisela
AU  - Angel, Peter
AU  - Bellusci, Saverio
AU  - Brinckmann, Jürgen
AU  - Auf dem Keller, Ulrich
AU  - Werner, Sabine
AU  - Bordoli, Mattia R
TI  - Mesenchyme-derived vertebrate lonesome kinase controls lung organogenesis by altering the matrisome.
JO  - Cellular and molecular life sciences
VL  - 80
IS  - 4
SN  - 1420-682X
CY  - Cham (ZG)
PB  - Springer International Publishing AG
M1  - DKFZ-2023-00536
SP  - 89
PY  - 2023
N1  - DKFZ-ZMBH Alliance
AB  - 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.
KW  - Collagen (Other)
KW  - Lung organogenesis (Other)
KW  - Pkdcc (Other)
KW  - Proteomics (Other)
KW  - Skull (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:36920550
DO  - DOI:10.1007/s00018-023-04735-6
UR  - https://inrepo02.dkfz.de/record/274322
ER  -