Naslov
Mapping the Phospho-dependent ALK Interactome to Identify Novel Components in ALK Signaling

Autori
Aboualizadeh, Farzaneh ; Yao, Zhong ; Guan, Jikui ; Drecun, Luka ; Pathmanathan, Shivanthy ; Snider, Jamie ; Umapathy, Ganesh ; Kotlyar, Max ; Jurisica, Igor ; Palmer, Ruth ; Stagljar, Igor

Izvornik
Journal of Molecular Biology (0022-2836) 433 (2021), 23; 167283, 10

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
RECEPTOR TYROSINE KINASE ; ANAPLASTIC LYMPHOMA KINASE ; LUNG-CANCER ; NPM-ALK ; PROTEINS ; ADAPTER ; IDENTIFICATION ; COMPLEMENT ; EXPRESSION ; PATHWAYS

Sažetak
Protein-protein interactions (PPIs) play essential roles in Anaplastic Lymphoma Kinase (ALK) signaling. Systematic characterization of ALK interactors helps elucidate novel ALK signaling mechanisms and may aid in the identification of novel therapeutics targeting related diseases. In this study, we used the Mammalian Membrane Two- Hybrid (MaMTH) system to map the phospho-dependent ALK interactome. By screening a library of 86 SH2 domain-containing full length proteins, 30 novel ALK interactors were identified. Many of their interactions are correlated to ALK phosphorylation activity: oncogenic ALK mutations potentiate the interactions and ALK inhibitors attenuate the interactions. Among the novel interactors, NCK2 was further verified in neuroblastoma cells using co-immunoprecipitation. Modulation of ALK activity by addition of inhibitors lead to concomitant changes in the tyrosine phosphorylation status of NCK2 in neuroblastoma cells, strongly supporting the functionality of the ALK/NCK2 interaction. Our study provides a resource list of potential novel ALK signaling components for further study. (C) 2021 The Authors. Published by Elsevier Ltd.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

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