Characterization of a phosphorylated form of the intermediate filament-aggregating protein filaggrin

Biochemistry. 1982 Nov 9;21(23):5940-8. doi: 10.1021/bi00266a033.

Abstract

Filaggrin and a phosphorylated form of filaggrin, which has been shown by pulse-chase studies to be a precursor form of the protein [Dale, B. A., & Ling, S. Y. (1979) Biochemistry 18, 3539-3546], were compared for functional, biochemical, and physical properties. Filaggrin reacts with keratin filaments to form visible macrofibrils, unlike the precursor which does not. Biochemical and peptide-mapping studies suggest that the two proteins have similar, perhaps identical, amino acid sequences. The major differences between the two proteins are in molecular weight (precursor, 44 200 g/mol; filaggrin, 38 400 g/mol), the existence of oligomeric forms of the precursor, and the presence of phosphate in the precursor (15-20 mol/mol of protein). Phosphoserine was identified in the precursor, but neither phosphothreonine nor phosphotyrosine was observed. The results of proteolytic digests of [32P]phosphate-radiolabeled precursor show that the phosphate is unevenly distributed throughout the molecule and may be localized in approximately 30% of the precursor. A discrete localization of the phosphate in the precursor may block a specific keratin filament combining site and so prevent premature aggregation of these filaments during epidermal differentiation. It is suggested that a specific phosphatase is involved in the dephosphorylation, because several phosphatases of general specificity, including rat epidermal lysosomal acid phosphatase, did not catalyze this conversion.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acids / analysis
  • Animals
  • Intermediate Filament Proteins / analysis
  • Intermediate Filament Proteins / metabolism*
  • Keratins / metabolism
  • Molecular Weight
  • Peptide Fragments / analysis
  • Phosphates / analysis
  • Phosphoric Monoester Hydrolases / metabolism
  • Phosphorylation
  • Protein Precursors / analysis
  • Protein Precursors / metabolism*
  • Rats

Substances

  • Amino Acids
  • Intermediate Filament Proteins
  • Peptide Fragments
  • Phosphates
  • Protein Precursors
  • filaggrin
  • Keratins
  • Phosphoric Monoester Hydrolases