B cell linker protein (BLNK) is a regulator of Met receptor signaling and trafficking in non-small cell lung cancer.

Abstract

Met is an oncogene aberrantly activated in multiple cancers. Therefore, to better understand Met biology and its role in disease we applied the Mammalian Membrane Two-Hybrid (MaMTH) to generate a targeted interactome map of its interactions with human SH2/PTB-domain-containing proteins. We identified thirty interaction partners, including sixteen that were previously unreported. Non-small cell lung cancer (NSCLC)-focused functional characterization of a Met-interacting protein, BLNK, revealed that BLNK is a positive regulator of Met signaling, and modulates localization, including ligand-dependent trafficking of Met in NSCLC cell lines. Furthermore, the interaction between Met and GRB2 is increased in the presence of BLNK, and the constitutive interaction between BLNK and GRB2 is increased in the presence of active Met. Tumor phenotypical assays uncovered roles for BLNK in anchorage-independent growth and chemotaxis of NSCLC cell lines. Cumulatively, this study provides a Met-interactome and delineates a role for BLNK in regulating Met biology in NSCLC context.

• Authors: Shivanthy Pathmanathan, Zhong Yao, Paula Coelho, Robert Valla, Luka Drecun, Caroline Benz, Jamie Snider, Punit Saraon, Ingrid Grozavu, Max Kotlyar, Igor Jurisica, Morag Park, Igor Stagljar
• Journal: iScience (iScience) Vol. 25 Issue 11 Pg. 105419 (Nov 18 2022) ISSN: 2589-0042 [Electronic] United States
• PMID: 36388990 (Publication Type: Journal Article)
• Copyright: © 2022 The Authors.