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Kinome profiling of Nf2-null murine Schwann cell line MS03 with defactinib and VS-4718

ABSTRACT: Patients with neurofibromatosis type 2-related schwannomatosis (NF2-SWN) develop hallmark tumors on their vestibular nerves, leading to hearing loss and numerous associated morbidities. Currently, there are no targeted therapeutic options for treating these tumors. In prior work, our group had identified brigatinib as a potentially active drug in the treatment of murine models of NF2-SWN and meningioma, leading to a clinical trial in NF2-SWN patients testing brigatinib. Kinome profiling revealed that brigatinib resulted in the inhibition of focal adhesion kinase 1 (FAK1, encoded by the PTK2 gene). To test the contribution of FAK1, we generated a genetically engineered mouse model of NF2-SWN with Fak1/Ptk2 deletion in tumorigenic cells of origin. Genetic ablation of Fak1/Ptk2 preserved hearing in the mice and reduced tumorigenesis. Here we used an immortalized Nf1 null Schwann cell line, MS03, to perform kinome profiling using the FAK inhibitors defactinib and VS-4718. Kinase enrichment proteomic analysis was performed using MS03 cells treated for 24 h with DMSO control, 1 micromolar defactinib, or 1 micromolar VS-4718 to evaluate the effects on the functional kinome.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

SUBMITTER: Steven Angus

LAB HEAD: D. Wade Clapp, MD

PROVIDER: PXD060730 | Pride | 2025-09-17

REPOSITORIES: Pride

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			Action	DRS
	KinomeMetadata.MS03.FAK.xlsx	Xlsx
	MSO3_DEF_1.raw	Raw
	MSO3_DEF_2.raw	Raw
	MSO3_DEF_3.raw	Raw
	MSO3_DMSO_1.raw	Raw

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