The intermediate filament protein keratin 8 is a novel cytoplasmic substrate for c-Jun N-terminal kinase

J Biol Chem. 2002 Mar 29;277(13):10767-74. doi: 10.1074/jbc.M111436200. Epub 2002 Jan 7.


Keratins 8 (K8) and 18 are the primary intermediate filaments of simple epithelia. Phosphorylation of keratins at specific sites affects their organization, assembly dynamics, and their interaction with signaling molecules. A number of keratin in vitro and in vivo phosphorylation sites have been identified. One example is K8 Ser-73, which has been implicated as an important phosphorylation site during mitosis, cell stress, and apoptosis. We show that K8 is strongly phosphorylated on Ser-73 upon stimulation of the pro-apoptotic cytokine receptor Fas/CD95/Apo-1 in HT-29 cells. Kinase assays showed that c-Jun N-terminal kinase (JNK) was also activated with activation kinetics corresponding to that of K8 phosphorylation. Furthermore, K8 was also phosphorylated on Ser-73 by JNK in vitro, yielding similar phosphopeptide maps as the in vivo phosphorylated material. In addition, co-immunoprecipitation studies revealed that part of JNK is associated with K8 in vivo, correlating with decreased ability of JNK to phosphorylate the endogenous c-Jun. Taken together, K8 is a new cytoplasmic target for JNK in Fas receptor-mediated signaling. The functional significance of this phosphorylation could relate to regulation of JNK signaling and/or regulation of keratin dynamics.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Bacterial Proteins*
  • Cell Line
  • Cytoplasm / metabolism*
  • Humans
  • JNK Mitogen-Activated Protein Kinases
  • Keratin-8
  • Keratins / chemistry
  • Keratins / metabolism*
  • Mitogen-Activated Protein Kinases / metabolism*
  • Molecular Sequence Data
  • Phosphorylation
  • Sequence Homology, Amino Acid
  • Serine / metabolism
  • Substrate Specificity
  • Transcription Factors / metabolism


  • Bacterial Proteins
  • FasR protein, Rhodococcus fascians
  • KRT8 protein, human
  • Keratin-8
  • Transcription Factors
  • Serine
  • Keratins
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinases