Multiplexed Kinase Interactome Profiling Quantifies Cellular Network Activity and Plasticity

Overview

Journal Mol Cell

Publisher Cell Press

Specialty Cell Biology

Date 2023 Feb 3

PMID 36736316

Authors

Martin Golkowski

Andrea Lius

Tanmay Sapre

Ho-Tak Lau

Taylor Moreno

Dustin J Maly

Shao-En Ong

Affiliations

Soon will be listed here.

Abstract

Dynamic changes in protein-protein interaction (PPI) networks underlie all physiological cellular functions and drive devastating human diseases. Profiling PPI networks can, therefore, provide critical insight into disease mechanisms and identify new drug targets. Kinases are regulatory nodes in many PPI networks; yet, facile methods to systematically study kinase interactome dynamics are lacking. We describe kinobead competition and correlation analysis (kiCCA), a quantitative mass spectrometry-based chemoproteomic method for rapid and highly multiplexed profiling of endogenous kinase interactomes. Using kiCCA, we identified 1,154 PPIs of 238 kinases across 18 diverse cancer lines, quantifying context-dependent kinase interactome changes linked to cancer type, plasticity, and signaling states, thereby assembling an extensive knowledgebase for cell signaling research. We discovered drug target candidates, including an endocytic adapter-associated kinase (AAK1) complex that promotes cancer cell epithelial-mesenchymal plasticity and drug resistance. Our data demonstrate the importance of kinase interactome dynamics for cellular signaling in health and disease.

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