Bryostatin-1 enhances barrier function in T84 epithelia through PKC-dependent regulation of tight junction proteins

James Yoo, Anthony Nichols, Joshua Mammen, Isabel Calvo, Jaekyung C. Song, Roger T. Worrell, Karl Matlin, Jeffrey B. Matthews

Research output: Contribution to journalArticlepeer-review

50 Scopus citations

Abstract

Protein kinase C (PKC) is known to regulate epithelial barrier function. However, the effect of specific PKC isozymes, and their mechanism of action, are largely unknown. We determined that the nonphorbol ester PKC agonist bryostatin-1 increased transepithelial electrical resistance (TER), a marker of barrier function, in confluent T84 epithelia. Bryostatin-1, which has been shown to selectively activate PKC-α, ε, and δ (34), was associated with a shift in the subcellular distribution of the tight junction proteins claudin-1 and ZO-2 from a detergent-soluble fraction into a detergent-insoluble fraction. Bryostatin-1 also led to the appearance of a higher-molecular-weight form of occludin previously shown to correspond to protein phosphorylation. These changes were attenuated by the conventional and novel PKC inhibitor Gö-6850 but not the conventional PKC inhibitor Gö-6976 or the PKC-δ inhibitor röttlerin, implicating a novel isozyme, likely PKC-ε. The results suggest that enhanced epithelial barrier function induced by bryostatin-1 involves a PKC-ε-dependent signaling pathway leading to recruitment of claudin-1 and ZO-2, and phosphorylation of occludin, into the tight junctional complex.

Original languageEnglish (US)
Pages (from-to)C300-C309
JournalAmerican Journal of Physiology - Cell Physiology
Volume285
Issue number2 54-2
DOIs
StatePublished - Aug 1 2003
Externally publishedYes

Keywords

  • Epithelial barrier function
  • Protein kinase C

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

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