Journal Article

DKFZ-2023-00536

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Mesenchyme-derived vertebrate lonesome kinase controls lung organogenesis by altering the matrisome.

Brütsch, S. M. ; Madzharova, E. ; Pantasis, S. ; Wüstemann, T. ; Gurri, S. ; Steenbock, H. ; Gazdhar, A. ; Kuhn, G. ; Angel, P.DKFZ* ; Bellusci, S. ; Brinckmann, J. ; Auf dem Keller, U. ; Werner, S. ; Bordoli, M. R.

2023
Springer International Publishing AG Cham (ZG)

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Please use a persistent id in citations: doi:10.1007/s00018-023-04735-6

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.

Keyword(s): Collagen ; Lung organogenesis ; Pkdcc ; Proteomics ; Skull

Note: DKFZ-ZMBH Alliance

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Contributing Institute(s):

1. A100 Signaltransduktion/ Wachstumskontrolle (A100)

Research Program(s):

1. 311 - Zellbiologie und Tumorbiologie (POF4-311) (POF4-311)

Appears in the scientific report 2023

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Database coverage:
; BIOSIS Previews ; BIOSIS Reviews Reports And Meetings ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; SCOPUS ; Web of Science Core Collection

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