Soluble form of Jagged1: unique product of epithelial keratinocytes and a regulator of keratinocyte differentiation

J Cell Biochem. 2004 Aug 15;92(6):1271-81. doi: 10.1002/jcb.20125.

Abstract

Notch signaling pathway is an important regulator of epithelial differentiation. Recent studies have characterized multiple ligands, including Jagged1, as mediators of Notch signaling. In this work, an alternatively spliced transcript of Jagged1 was isolated in yeast two-hybrid screening through interaction with thrombospondin-1. This transcript, devoid of sequences encoding the transmembrane and intracellular domains of Jagged1, was specific for keratinocytes. Furthermore, the truncated Jagged1 polypeptide devoid of the intracellular domain was detected prominently in the suprabasal keratinocyte layer in neonatal epithelia. The soluble form of Jagged1, when expressed as a tagged polypeptide was efficiently secreted into the culture medium and the N-terminal signal sequence became cleaved off upon secretion. Direct contact between a cell presenting the transmembrane form of Jagged1 and a Notch-expressing cell has been proposed as a prerequisite for the signaling event. However, the soluble form of Jagged1, when present in the cell culture medium, was sufficient to induce keratinocyte differentiation. These observations suggest a novel mechanism of how Jagged1 can target cells beyond the direct cell-cell contact in developing epithelia.

Publication types

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

MeSH terms

  • Alternative Splicing
  • Animals
  • Base Sequence
  • Blotting, Western
  • Calcium-Binding Proteins
  • Cell Differentiation / physiology*
  • Cell Line
  • Culture Media
  • DNA Primers
  • Dogs
  • Epithelial Cells / cytology
  • Epithelial Cells / metabolism
  • Humans
  • Intercellular Signaling Peptides and Proteins
  • Jagged-1 Protein
  • Keratinocytes / metabolism*
  • Membrane Proteins
  • Protein Binding
  • Proteins / genetics
  • Proteins / metabolism*
  • Proteins / physiology
  • RNA, Messenger / genetics
  • Serrate-Jagged Proteins
  • Thrombospondin 1 / metabolism

Substances

  • Calcium-Binding Proteins
  • Culture Media
  • DNA Primers
  • Intercellular Signaling Peptides and Proteins
  • JAG1 protein, human
  • Jagged-1 Protein
  • Membrane Proteins
  • Proteins
  • RNA, Messenger
  • Serrate-Jagged Proteins
  • Thrombospondin 1