Type I keratin 17 protein is phosphorylated on serine 44 by p90 ribosomal protein S6 kinase 1 (RSK1) in a growth- and stress-dependent fashion

Xiaoou Pan, Lesley A. Kane, Jennifer E. Van Eyk, Pierre A. Coulombe

Research output: Contribution to journalArticle


Keratin 17 (K17) is a type I intermediate filament protein that is constitutively expressed in ectoderm-derived epithelial appendages and robustly induced in epidermis following injury, during inflammation, and in chronic diseases such as psoriasis and cancer. Mutations within K17 are responsible for two rare diseases related to ectodermal dysplasias. Studies in K17-null mice uncovered several roles for K17, including structural support, resistance to TNFα-induced apoptosis, regulation of protein synthesis, and modulation of cytokine expression. Yet, little is known about the regulation of K17 protein via post-translational modification. Here, we report that serine 44 in the N-terminal head domain of K17 (K17-Ser 44) is phosphorylated in response to extracellular stimuli (serum, EGF, and the phorbol ester 12-O-tetradecanoylphorbol-13-acetate) that alter skin keratinocyte growth, and to cellular stresses (sorbitol-induced hyperosmotic shock, UV irradiation, and hydrogen peroxide-induced oxidative stress). It also occurs in basaloid skin tumors in situ. Upon its stimulation in skin keratinocytes, K17-Ser 44phosphorylation is induced rapidly but stays on transiently. The majority of the phosphorylated K17-Ser 44 pool is polymerbound and is not obviously related to a change in filament organization. The amino acid sequence surrounding K17-Ser 44matches the consensus for the AGC family of basophilic kinases. We show that p90 RSK1, an AGC kinase involved in the regulation of cell survival and proliferation, phosphorylates K17-Ser 44in skin keratinocytes. These findings confirm and expand the tight link that has emerged between K17 up-regulation and growth and stress responses in the skin epithelium.

Original languageEnglish (US)
Pages (from-to)42403-42413
Number of pages11
JournalJournal of Biological Chemistry
Issue number49
StatePublished - Dec 9 2011

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Type I keratin 17 protein is phosphorylated on serine 44 by p90 ribosomal protein S6 kinase 1 (RSK1) in a growth- and stress-dependent fashion'. Together they form a unique fingerprint.

  • Cite this