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Previously, we discovered that the Thr\n                    <jats:sup>335<\/jats:sup>\n                    \u2010Pro motif within the PKC\u03b8\u2010V3 regulatory domain serves as a critical site for PKC\u03b8 activation and demonstrated that phosphorylation of the Thr\n                    <jats:sup>335<\/jats:sup>\n                    \u2010Pro motif creates a binding site for the peptidyl\u2010prolyl\n                    <jats:italic>cis\u2010trans<\/jats:italic>\n                    isomerase (PPIase), Pin1. Herein, we elaborate on the functional consequences of the Pin1\u2010PKC\u03b8 association and identify Pin1 as a regulator of PKC\u03b8 catalytic activity. Pin1 downregulated the activity of PKC\u03b8 in vitro in PMA\u2010stimulated human Jurkat T cells and C57BL\/6J mouse spleen\u2010 and thymus\u2010derived T lymphocytes, an effect that was reversed by juglone, a Pin1\u2010activity inhibitor. Utilizing Pin1 isomerase\u2010deficient mutants, we demonstrate that the functionality of the Pin1 catalytic domain is essential for its regulation of PKC\u03b8, suggesting that Pin1 mediates its inhibitory effect on PKC\u03b8 via\n                    <jats:italic>cis\u2010trans<\/jats:italic>\n                    isomerization. In silico docking analysis supported the role of critical residues within the Pin1\u2010PPIase domain that enables the\n                    <jats:italic>cis\u2010trans<\/jats:italic>\n                    interconversion of the PKC\u03b8 phospho\u2010Thr\n                    <jats:sup>335<\/jats:sup>\n                    \u2010Pro motif. Retroviral knockdown of Pin1 in Jurkat T cells led to an elevation in PKC\u03b8 kinase activity. Furthermore, stimulation of [Lck\n                    <jats:sup>cre<\/jats:sup>\n                    \u00d7 Pin1\n                    <jats:sup>lox<\/jats:sup>\n                    ] F\n                    <jats:sub>1<\/jats:sub>\n                    mice\u2010derived Pin1\u2010deficient T cells augmented the phosphorylation of SPAK kinase, a bona fide PKC\u03b8 downstream substrate. Together, our results support a role for the Pin1 isomerase as a regulator of PKC\u03b8 activity and highlight the potential contribution of Pin1 to the fine\u2010tuning of the T cell activation dynamics.\n                  <\/jats:p>","DOI":"10.1002\/pro.70414","type":"journal-article","created":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T14:00:15Z","timestamp":1766412015000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The peptidyl\u2010prolyl\n                    <i>cis\u2010trans<\/i>\n                    isomerase, Pin1, is a regulator of the protein kinase C \u03b8 (\n                    <scp>PKC\u03b8<\/scp>\n                    ) catalytic activity in activated T cells"],"prefix":"10.1002","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9449-5654","authenticated-orcid":false,"given":"Nikhil Ponnoor","family":"Anto","sequence":"first","affiliation":[{"name":"The Shraga Segal Department of Microbiology, Immunology and Genetics Faculty of Health Sciences, Ben\u2010Gurion University of the Negev  Beer Sheva Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5825-6514","authenticated-orcid":false,"given":"Amitha","family":"Muraleedharan","sequence":"additional","affiliation":[{"name":"The Shraga Segal Department of Microbiology, Immunology and Genetics Faculty of Health Sciences, Ben\u2010Gurion University of the Negev  Beer Sheva Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Divya Ram","family":"Jayaram","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital Cancer Center  Boston Massachusetts USA"},{"name":"Department of Medicine Harvard Medical School  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8452-1759","authenticated-orcid":false,"given":"Vijayasteltar Belsamma","family":"Liju","sequence":"additional","affiliation":[{"name":"The Shraga Segal Department of Microbiology, Immunology and Genetics Faculty of Health Sciences, Ben\u2010Gurion University of the Negev  Beer Sheva Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0554-4176","authenticated-orcid":false,"given":"Jakeer","family":"Shaik","sequence":"additional","affiliation":[{"name":"The Shraga Segal Department of Microbiology, Immunology and Genetics Faculty of Health Sciences, Ben\u2010Gurion University of the Negev  Beer Sheva Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9737-1849","authenticated-orcid":false,"given":"James","family":"Malter","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Texas Southwestern Medical Center  Dallas Texas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0994-1520","authenticated-orcid":false,"given":"Chen","family":"Keasar","sequence":"additional","affiliation":[{"name":"The Department of Computer Science Ben\u2010Gurion University of the Negev  Beer Sheva Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5270-6679","authenticated-orcid":false,"given":"Etta","family":"Livneh","sequence":"additional","affiliation":[{"name":"The Shraga Segal Department of Microbiology, Immunology and Genetics Faculty of Health Sciences, Ben\u2010Gurion University of the Negev  Beer Sheva Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2802-1148","authenticated-orcid":false,"given":"Alex","family":"Braiman","sequence":"additional","affiliation":[{"name":"The Shraga Segal Department of Microbiology, Immunology and Genetics Faculty of Health Sciences, Ben\u2010Gurion University of the Negev  Beer Sheva Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0717-5367","authenticated-orcid":false,"given":"Amnon","family":"Altman","sequence":"additional","affiliation":[{"name":"Center for Cancer Immunotherapy La Jolla Institute for Immunology  La Jolla California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kok\u2010Fai","family":"Kong","sequence":"additional","affiliation":[{"name":"Division of Cell Biology La Jolla Institute for Immunology  La Jolla California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1412-0957","authenticated-orcid":false,"given":"Noah","family":"Isakov","sequence":"additional","affiliation":[{"name":"The Shraga Segal Department of Microbiology, Immunology and Genetics Faculty of Health Sciences, Ben\u2010Gurion University of the Negev  Beer Sheva 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