Dataset Information

Quantitative proteomics analysis of lung tissue from E18.5 embryos with mesenchymal deletion of VLK

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 with a mesenchyme-specific knockout of the VLK gene (protein kinase domain containing, cytoplasmic (Pkdcc)). Most of the homozygous mice die 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 112 proteins with significantly and at least 1.5fold 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 non-cell-autonomous modulation of alveolar epithelial cell differentiation.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Embryo, Lung

SUBMITTER: Ulrich auf dem Keller

LAB HEAD: Ulrich auf dem Keller

PROVIDER: PXD037700 | Pride | 2023-04-11

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	20200303_MB_FS_EVO_Eli_lung_NPO.msf	Msf
	20200303_MB_FS_EVO_Eli_lung_NPO.mzML	Mzml
	20200303_MB_FS_EVO_Eli_lung_NPO.mzid.gz	Mzid
	20200303_MB_FS_EVO_Eli_lung_NPO1.raw	Raw
	20200303_MB_FS_EVO_Eli_lung_NPO10.raw	Raw

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Publications

Mesenchyme-derived vertebrate lonesome kinase controls lung organogenesis by altering the matrisome.

Brütsch Salome M SM Madzharova Elizabeta E Pantasis Sophia S Wüstemann Till T Gurri Selina S Steenbock Heiko H Gazdhar Amiq A Kuhn Gisela G Angel Peter P Bellusci Saverio S Brinckmann Jürgen J Auf dem Keller Ulrich U Werner Sabine S Bordoli Mattia R MR

Cellular and molecular life sciences : CMLS 20230315 4

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 ...[more]

PMID: 36920550

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