Proteomic analysis of tyrosine phosphorylation induced by exogenous expression of oncogenic kinase fusions identified in lung adenocarcinoma

  • Kinase fusions are considered oncogenic drivers in numerous types of cancer. In lung adenocarcinoma 5–10% of patients harbor kinase fusions. The most frequently detected kinase fusion involves the Anaplastic Lymphoma Kinase (ALK) and Echinoderm Microtubule-associated protein-Like 4 (EML4). In addition, oncogenic kinase fusions involving the tyrosine kinases RET and ROS1 are found in smaller subsets of patients. In this study, we employed quantitative mass spectrometry-based phosphoproteomics to define the cellular tyrosine phosphorylation patterns induced by different oncogenic kinase fusions identified in patients with lung adenocarcinoma. We show that exogenous expression of the kinase fusions in HEK 293T cells leads to widespread tyrosine phosphorylation. Direct comparison of different kinase fusions demonstrates that the kinase part and not the fusion partner primarily defines the phosphorylation pattern. The tyrosine phosphorylation patterns differed between ALK, ROS1, and RET fusions, suggesting that oncogenic signaling induced by these kinases involves the modulation of different cellular processes.
Author:Sebastian Alexander WagnerORCiDGND, Pawel P. Szczesniak, Andrea Voigt, Justus F. Gräf, Petra BeliORCiDGND
Parent Title (English):Proteomics
Publisher:Wiley VCH
Place of publication:Weinheim
Document Type:Article
Date of Publication (online):2021/03/25
Date of first Publication:2021/03/25
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2021/09/08
Tag:ALK; RET; ROS1; fusion kinase; lung cancer; phosphoproteomics
Issue:10, art. 2000283
Page Number:12
First Page:1
Last Page:12
The support of the IMB Microscopy Core Facility is gratefully acknowledged. Petra Beli was supported by the Emmy Noether Program (BE 5342/1-1). Sebastian A. Wagner was supported by the LOEWE program Ubiquitin Networks (Ub-Net) of the State of Hesse (Germany), the Else Kröner-Fresenius-Stiftung (2015_A124) and the Else Kröner-Forschungskolleg Frankfurt. The usage of Proteomics and Microscopy core facilities at IMB is gratefully acknowledged.

Open access funding enabled and organized by Projekt DEAL.
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung 4.0