Multiple PKCδ tyrosine residues are required for PKCδ-dependent activation of involucrin expression - A key role of PKCδ-Y311

Ling Zhu, Chaya Brodie, Sivaprakasam Balasubramanian, Richard L. Eckert

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9 Scopus citations


Protein kinase C-delta (PKCδ) is a key regulator of human involucrin (hINV) gene expression and is regulated by tyrosine phosphorylation. However, a comprehensive analysis of the requirement for individual PKCδ tyrosine residues is lacking. We show that multiple tyrosine residues influence the ability of PKCδ to increase hINV gene expression. Mutation of individual PKCδ tyrosine residues 52, 64, 155, 187, or 565 does not reduce the ability of PKCδ to increase hINV promoter activity; however, simultaneous mutation of these five tyrosines markedly reduces activity. Moreover, restoration of any one of these residues results in nearly full activity restoration. It is significant that phosphorylation of PKCδ-Y 311 is reduced in the five-tyrosine mutant and that mutation of Y311 results in reduced PKCδ activity comparable to that observed in the five-tyrosine mutant. Restoration of any one of the tyrosine residues in the five-tyrosine mutant restores Y311 phosphorylation and biological activity. In addition, reduced phosphorylation of endogenous PKCδ-Y311 is associated with reduced biological activity. These findings indicate that PKCδ activity requires Y311 and a second tyrosine residue; however, any one of the several tyrosine residues can serve in the secondary role.

Original languageEnglish
Pages (from-to)833-845
Number of pages13
JournalJournal of Investigative Dermatology
Issue number4
StatePublished - Apr 2008
Externally publishedYes

Bibliographical note

Funding Information:
This work utilized the facilities of the Skin Diseases Research Center of Northeast Ohio (NIH, AR39750) and was supported by grants to R.L.E. (RO1AR046494) and C.B. (RO1CA109196) from the National Institutes of Health.


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