Receptor-proximal phosphoform organization precedes β2 integrin activation
- 1The University of Texas Health Science Center at Houston
Abstract
Receptor signaling is often framed as protein recruitment after stimulation, but whether receptor-proximal environments are organized in composition and phosphorylation state beforehand remains unclear. We used CD18-APEX2 proximity labeling and a spatial membrane reference to quantify proteins and phosphosites near leukocyte {beta}2 integrins. At rest, receptors, adaptors and Rap GTPases were preferentially represented relative to several catalytic classes. Parent-protein correction revealed spatial phosphoform organization, with 32% of 4,564 phosphosites deviating significantly from the distribution center and 56% of proteins with multiple quantified sites showing divergence beyond measurement error. Sustained activation altered 31% of phosphosites while 95.9% of proteins remained equivalent within {+/-}0.5 log2 and spatial phosphoform organization largely persisted. Most phosphorylation responses were shared across both labeling environments, whereas receptor-preferential changes were dominated by phosphosites. These findings suggest that receptor signaling can regulate pre-existing molecular states without extensive protein redistribution.
Related
- 294 Flotillin-2 shapes CD8+ T cell anti-tumor immunity through T cell receptor spatial organization
- Endogenous retrovirus activation disrupts postsynaptic organization in human glutamatergic neurons
- DNA replication is dispensable for developmental progression, but required for heterochromatin organization at mouse zygotic genome activation
- Activation of α7 Nicotinic Acetylcholine Receptor Inhibits Neutrophil ex vivo Swarming and Pulmonary Recruitment in Inflamed Mice through an Integrin αMβ2-dependent Mechanism
- On-virion structural dynamics reveal temperature- and receptor-coordinated activation of an alphacoronavirus spike
BibTeX
@misc{moore2026receptorproximal,
title = {{Receptor-proximal phosphoform organization precedes β2 integrin activation}},
author = {T. I. Moore and N. A. Hummell and H. Jonnagaddala and M. Kalocsay},
howpublished = {bioRxiv},
year = {2026},
month = nov,
doi = {10.64898/2026.11.04.762546},
url = {https://www.biorxiv.org/content/10.64898/2026.11.04.762546v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Receptor-proximal phosphoform organization precedes β2 integrin activation
AU - T. I. Moore
AU - N. A. Hummell
AU - H. Jonnagaddala
AU - M. Kalocsay
PY - 2026
DA - 2026/11/04
PB - bioRxiv
DO - 10.64898/2026.11.04.762546
UR - https://www.biorxiv.org/content/10.64898/2026.11.04.762546v1
AB - Receptor signaling is often framed as protein recruitment after stimulation, but whether receptor-proximal environments are organized in composition and phosphorylation state beforehand remains unclear. We used CD18-APEX2 proximity labeling and a spatial membrane reference to quantify proteins and phosphosites near leukocyte {beta}2 integrins. At rest, receptors, adaptors and Rap GTPases were preferentially represented relative to several catalytic classes. Parent-protein correction revealed spatial phosphoform organization, with 32% of 4,564 phosphosites deviating significantly from the distribution center and 56% of proteins with multiple quantified sites showing divergence beyond measurement error. Sustained activation altered 31% of phosphosites while 95.9% of proteins remained equivalent within {+/-}0.5 log2 and spatial phosphoform organization largely persisted. Most phosphorylation responses were shared across both labeling environments, whereas receptor-preferential changes were dominated by phosphosites. These findings suggest that receptor signaling can regulate pre-existing molecular states without extensive protein redistribution.
ER -