Unravelling the Phosphorylation Landscape of Anthrax Toxin Receptor 1: Mechanisms and Functional Insights Through Phosphoproteomic Data Integration

Abstract

Anthrax Toxin Receptor 1 (ANTXR1) is a transmembrane protein involved in various biological processes, including angiogenesis, cell adhesion, and migration. As a receptor for Bacillus anthracis toxins and the oncolytic Seneca Valley virus, ANTXR1 plays pivotal roles in extracellular matrix interactions, actin cytoskeleton organization, and tumor progression. Despite its relevance in cancer biology, ANTXR1 remains understudied from a phosphoproteomics perspective. In this study, we report the phosphoproteomic landscape of the ANTXR1 protein through a unique data integration strategy from a mass spectrometry-based phosphoproteomics perspective. Through robust statistical analyses, conserved phosphorylation events of ANTXR1 across diverse experimental conditions were linked to its upstream kinases and binary interactors to deduce specific events modulated through ANTXR1 phosphorylation. This computational analysis of curated datasets identified conserved ANTXR1 phosphorylation events along with similar and oppositely co-regulated phosphorylation events of adjunct proteins, revealing extensive regulatory networks of ANTXR1. Our findings provide phosphorylation-dependent interaction between ANTXR1 and FLNA and their upstream kinases and phosphobinding motifs, emphasizing their collective role in cell migration. Overall, the study enhances the integrative analysis of mass spectrometry-based phosphoproteomics data through bioinformatics and statistical approaches.