Occludin is hyperphosphorylated on Ser and Thr residues in intact epithelial tight junctions. The dynamics of epithelial tight junctions appear to involve reversible phosphorylation of occludin on Ser and Thr residues. In the present study we determined the role of PKCζ in occludin phosphorylation and the dynamics of tight junctions. Inhibition of PKCζ by specific PKCζ pseudo substrate rapidly reduced TER, increased inulin permeability and induced redistribution of occludin and ZO‑1 in Caco‑2 and MDCK cell monolayers without inducing cytotoxicity. Reduced expression of PKCζ also resulted in compromised tight junction integrity. Both PKCζ pseudo substrate and reduced expression of PKCζ delayed the calcium-induced assembly of tight junctions. PKCζ pseudo substrate rapidly reduced occludin phosphorylation on Ser and Thr, and prevented Ser/Thr phosphorylation of occludin during the assembly of tight junctions. Pairwise binding studies showed that PKCζ directly bound to and phosphorylated the C‑terminal tail of occludin on Ser and Thr residues. Site directed point mutation demonstrated that PKCζ predominantly phosphorylated T438, but also phosphorylated T403 and T404. This study demonstrates that PKCζ phosphorylated occludin on Ser/Thr residues and regulated the assembly of tight junctions.
","abstract_html":"<p>Occludin is hyperphosphorylated on Ser and Thr residues in intact epithelial tight junctions. The dynamics of epithelial tight junctions appear to involve reversible phosphorylation of occludin on Ser and Thr residues. In the present study we determined the role of PKCζ in occludin phosphorylation and the dynamics of tight junctions. Inhibition of PKCζ by specific PKCζ pseudo substrate rapidly reduced TER, increased inulin permeability and induced redistribution of occludin and ZO‑1 in Caco‑2 and MDCK cell monolayers without inducing cytotoxicity. Reduced expression of PKCζ also resulted in compromised tight junction integrity. Both PKCζ pseudo substrate and reduced expression of PKCζ delayed the calcium-induced assembly of tight junctions. PKCζ pseudo substrate rapidly reduced occludin phosphorylation on Ser and Thr, and prevented Ser/Thr phosphorylation of occludin during the assembly of tight junctions. Pairwise binding studies showed that PKCζ directly bound to and phosphorylated the C‑terminal tail of occludin on Ser and Thr residues. Site directed point mutation demonstrated that PKCζ predominantly phosphorylated T438, but also phosphorylated T403 and T404. This study demonstrates that PKCζ phosphorylated occludin on Ser/Thr residues and regulated the assembly of tight junctions.</p>","abstract_has_math":false,"creators":["Jain, Suneet Kumar"],"institution":null,"degree_name":"Doctor of Philosophy (PhD)","degree_level":"Dissertation","degree_discipline":"Biomedical Sciences","degree_department":null,"school":null,"contributors":["Radhakrishna Rao, Ph.D."],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2011,"date_issued":"2011-05-01T07:00:00Z","date_published":"2011-05-01T07:00:00Z","updated_at":"2026-07-24T05:00:11Z","subjects":["Tight Junction","Occludin","ZO-1","PKC-zeta","Medical Biochemistry","Medical Sciences","Medicine and Health Sciences"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://dc.uthsc.edu/dissertations/117","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Radhakrishna Rao, Ph.D."]},{"key":"dc:creator","label":"Author","values":["Jain, Suneet Kumar"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.available","label":"Dc Date Available","values":["2016-06-08T07:00:00Z"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Biomedical Sciences"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Dissertation"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Doctor of Philosophy (PhD)"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Tight Junction","Occludin","ZO-1","PKC-zeta","Medical Biochemistry","Medical Sciences","Medicine and Health Sciences"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://dc.uthsc.edu/dissertations/117"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Occludin is hyperphosphorylated on Ser and Thr residues in intact epithelial tight junctions. The dynamics of epithelial tight junctions appear to involve reversible phosphorylation of occludin on Ser and Thr residues. In the present study we determined the role of PKCζ in occludin phosphorylation and the dynamics of tight junctions. Inhibition of PKCζ by specific PKCζ pseudo substrate rapidly reduced TER, increased inulin permeability and induced redistribution of occludin and ZO‑1 in Caco‑2 and MDCK cell monolayers without inducing cytotoxicity. Reduced expression of PKCζ also resulted in compromised tight junction integrity. Both PKCζ pseudo substrate and reduced expression of PKCζ delayed the calcium-induced assembly of tight junctions. PKCζ pseudo substrate rapidly reduced occludin phosphorylation on Ser and Thr, and prevented Ser/Thr phosphorylation of occludin during the assembly of tight junctions. Pairwise binding studies showed that PKCζ directly bound to and phosphorylated the C‑terminal tail of occludin on Ser and Thr residues. Site directed point mutation demonstrated that PKCζ predominantly phosphorylated T438, but also phosphorylated T403 and T404. This study demonstrates that PKCζ phosphorylated occludin on Ser/Thr residues and regulated the assembly of tight junctions.
"]},{"key":"dc:title","label":"Title","values":["Role of Protein Kinase C Zeta (PKCζ) in Regulation of Epithelial Tight Junctions"]}]}],"canonical_facts":{"dc:contributor":["Radhakrishna Rao, Ph.D."],"dc:creator":["Jain, Suneet Kumar"],"dc:date.available":["2016-06-08T07:00:00Z"],"dc:description.abstract":["Occludin is hyperphosphorylated on Ser and Thr residues in intact epithelial tight junctions. The dynamics of epithelial tight junctions appear to involve reversible phosphorylation of occludin on Ser and Thr residues. In the present study we determined the role of PKCζ in occludin phosphorylation and the dynamics of tight junctions. Inhibition of PKCζ by specific PKCζ pseudo substrate rapidly reduced TER, increased inulin permeability and induced redistribution of occludin and ZO‑1 in Caco‑2 and MDCK cell monolayers without inducing cytotoxicity. Reduced expression of PKCζ also resulted in compromised tight junction integrity. Both PKCζ pseudo substrate and reduced expression of PKCζ delayed the calcium-induced assembly of tight junctions. PKCζ pseudo substrate rapidly reduced occludin phosphorylation on Ser and Thr, and prevented Ser/Thr phosphorylation of occludin during the assembly of tight junctions. Pairwise binding studies showed that PKCζ directly bound to and phosphorylated the C‑terminal tail of occludin on Ser and Thr residues. Site directed point mutation demonstrated that PKCζ predominantly phosphorylated T438, but also phosphorylated T403 and T404. This study demonstrates that PKCζ phosphorylated occludin on Ser/Thr residues and regulated the assembly of tight junctions.
"],"dc:identifier":["https://dc.uthsc.edu/dissertations/117"],"dc:subject":["Tight Junction","Occludin","ZO-1","PKC-zeta","Medical Biochemistry","Medical Sciences","Medicine and Health Sciences"],"dc:title":["Role of Protein Kinase C Zeta (PKCζ) in Regulation of Epithelial Tight Junctions"],"thesis:degree_discipline":["Biomedical Sciences"],"thesis:degree_level":["Dissertation"],"thesis:degree_name":["Doctor of Philosophy (PhD)"]},"updated_at":"2026-07-24T05:00:11Z"}