ArticlebioRxiv : the preprint server for biology2024
Chemoproteomics reveals immunogenic and tumor-associated cell surface substrates of ectokinase CK2α.
Corleone S Delaveris, Sophie Kong, Jeff Glasgow, Rita P Loudermilk, Lisa L Kirkemo, Fangzhu Zhao, Fernando Salangsang, Paul Phojanakong, Juan Antonio Camara Serrano, Veronica Steri and 1 more
Open access · greenAbstract readPreprint
In one paragraphArticle in bioRxiv : the preprint server for biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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What it found
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5 · Who and what moneyAuthors and funding
11 authors at 1 institution in 1 country.
Corleone S DelaverisDepartment of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, California, 94158, USA.ORCID 0000-0002-7291-2338 Sophie KongDepartment of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, California, 94158, USA.
Jeff GlasgowDepartment of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, California, 94158, USA.ORCID 0000-0001-6699-8983 Rita P LoudermilkDepartment of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, California, 94158, USA.ORCID 0000-0001-9970-5112 Lisa L KirkemoDepartment of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, California, 94158, USA.ORCID 0000-0003-1686-6987 Fangzhu ZhaoDepartment of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, California, 94158, USA.ORCID 0000-0002-3172-1340 Fernando SalangsangPreclinical Therapeutics Core, Helen Diller Comprehensive Cancer Center, University of California San Francisco, San Francisco, California, 94158, USA.
Paul PhojanakongPreclinical Therapeutics Core, Helen Diller Comprehensive Cancer Center, University of California San Francisco, San Francisco, California, 94158, USA.
Juan Antonio Camara SerranoPreclinical Therapeutics Core, Helen Diller Comprehensive Cancer Center, University of California San Francisco, San Francisco, California, 94158, USA.
Veronica SteriPreclinical Therapeutics Core, Helen Diller Comprehensive Cancer Center, University of California San Francisco, San Francisco, California, 94158, USA.
James A WellsDepartment of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, California, 94158, USA.ORCID 0000-0001-8267-5519 University of California, San Francisco · US
Funding
Translational InformaticsP30CA082103 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Alan Ashworth · 1999 to 2026
$209.7MRenewable antibodies to secreted proteins and single and multi-pass cell surfaceP41CA196276 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MARKS, JAMES D. · 2014 to 2018
$5.8MAffinity-directed tagging of protein binding partners in signalingR01CA191018 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI WELLS, JAMES A · 2014 to 2018
$1.6MRegulating Proteolysis to Dissect ApoptosisR01GM097316 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI WELLS, JAMES A · 2011 to 2014
$1.1MMechanistic Insights and Diagnostic Applications for Hypoxia-Induced Vasorin in Pancreatic CancerF31CA247527 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI KIRKEMO, LISA · 2020 to 2022
$100kNCI NIH HHS F31 CA247527NCI NIH HHS P30 CA082103NCI NIH HHS P41 CA196276NCI NIH HHS R01 CA191018NIGMS NIH HHS R01 GM097316
6 · The paper itselfAbstract
New epitopes for immune recognition provide the basis of anticancer immunity. Due to the high concentration of extracellular adenosine triphosphate in the tumor microenvironment, we hypothesized that extracellular kinases (ectokinases) could have dysregulated activity and introduce aberrant phosphorylation sites on cell surface proteins. We engineered a cell-tethered version of the extracellular kinase CK2α, demonstrated it was active on cells under tumor-relevant conditions, and profiled its substrate scope using a chemoproteomic workflow. We then demonstrated that mice developed polyreactive antisera in response to syngeneic tumor cells that had been subjected to surface hyperphosphorylation with CK2α. Interestingly, these mice developed B cell and CD4+ T cell responses in response to these antigens but failed to develop a CD8+ T cell response. This work provides a workflow for probing the extracellular phosphoproteome and demonstrates that extracellular phosphoproteins are immunogenic even in a syngeneic system.
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PMID38562834
PMCPMC10983885
OpenAlexW4393053460
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